Apobec3b breast cancer

Last UpdatedMarch 5, 2024

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Oct 6, 2015 · Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. Cescon1,2,3* and Benjamin Haibe-Kains1,4,5,6* Abstract APOBEC cytidine deaminases have been implicated as major contributors to the mutation burden in many cancers on the basis of their mutational signature. Repair of APOBEC3B-induced lesions allows chromatin remodelling that stimulates gene expression. 13; p = 0. Aug 15, 2014 · The prognostic value of APOBEC3B was especially prominent in ER + disease, suggesting that particularly in this subclass of breast cancer levels of APOBEC3B may contribute to cancer progression. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines Nov 16, 2023 · We incor porate d ve breast cancer cell lines with doc umente d A3A and A3B expre ssion pro le s into this study [20], and gauged the act ivity of intrinsic A3B in the se lines. As efforts to develop APOBEC3 inhibitors progress, understanding the timing and consequences of APOBEC3-mediated mutagenesis in distinct clinical contexts will be critical for guiding the Dec 16, 2019 · Abstract. We classified breast cancers into three subtypes based on the expression of the estrogen receptor, progesterone Oct 1, 2021 · Recent studies in breast cancer identified that A3B mRNA is upregulated at the DCIS stage , but these studies did not investigate the entire repertoire of APOBEC3 genes. These insights provide support for therapeutic approaches that might limit the activity of this mutagenic process. APOBEC3B was upregulated by$3 s. Breast cancer genome and May 27, 2016 · Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. APOBEC3B is an enzymatic source of mutation in breast cancer. Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer. Here, we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Endogenous A3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing Jan 21, 2015 · A new example is the DNA cytosine deaminase APOBEC3B, which was identified recently as a source of DNA damage and mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser extents additional cancer types. Unlike for APOBEC3B, the significance in breast cancer of the other APOBEC3s, which too are capable DNA mutators, has remained unclear, and we sought to address this with our study. This phenomenon of clustered mutations, termed kataegis (from the Greek word for showers), forms unique mutation signatures. Roelofs PA, et al. Mar 3, 2015 · Genomic sequencing studies of breast and other cancers have identified patterns of mutations that have been attributed to the endogenous mutator activity of APOBEC3B (A3B), a member of the AID/APOBEC family of cytidine deaminases. Tumours that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53. Abstract. Similarly, mutational patterns associated with APOBEC de-regulation have been observed at the sites of translocations of the MYC gene in patients with multiple myeloma which occur in patients with very poor clinical outcomes Jul 14, 2013 · A total of ten cancers showed a median level of APOBEC3B upregulation greater than that of the intended positive control, breast cancer. Keywords: APOBEC3B, Asian, Breast cancer, Breast cancer risk, Immune response Background Apolipoprotein B mRNA-editing enzyme, catalytic Nov 11, 2016 · Also, APOBEC3B has recently been verified to be a marker of pure prognosis and poor outcomes for ER + breast cancer, which strongly suggests that genetic aberrations induced by APOBEC3B contribute to breast cancer progression . To investigate the clinical relevance of APOBEC3F expression, we analyzed a total of 3000 breast cancer cases from multiple independent large patient cohorts including METABRIC, TCGA, GSE75688, and GSE114725. Feb 15, 2022 · The role of APOBEC3A and APOBEC3B in breast cancer has been well described, whereas that of APOBEC3F remains unknown. In contrast to previous studies, APOBEC3B mRNA expression was not associated with breast cancer prognosis in patients receiving NAC. Kanu and colleagues focused on the association between replication stress and APOBEC3B activity in breast cancer cell lines, starting from the observation that the HER2-enriched subtype of breast cancers exhibits the greatest burden of APOBEC mutations [] and the premise that oncogene-induced replication stress exposes single-stranded DNA Apr 17, 2013 · Very few studies have evaluated copy number variation (CNV), another important source of human genetic variation, in relation to breast cancer risk. 2a). (A and B) A3B expression in relation to genotypes of the regulatory germline SNP rs17000526 in 387 ER+ and 116 ER− Nov 30, 2023 · cancer with particularly large contributions to tumors of the bladder, breast, cervix, lung, and head/neck. APOBEC3B is overexpressed in several human cancer types, including breast cancer. e. It Oct 15, 2021 · APOBEC enzymes are strong mutagenic factors. APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. In this study we link DNA replication stress mediated by oncogene activation or cytotoxic exposure to APOBEC3B activity. , mRNA levels 2- to 5-fold higher than those of the housekeeping gene TBP (6–8,14)]. Methods: We conducted a CNV GWAS in 2623 breast cancer patients and 1946 control subjects using data from Affymetrix SNP Array 6. However, breast cancers from polymorphism carriers do not display an increased number of APOBEC-mediated mutations [ 69 ]. Third, APOBEC3B overexpression accelerates the development of tamoxifen resistance in murine xenograft experiments by a mechanism that requires the enzyme’s catalytic activity. In this study, we evaluated the characteristics of a real-world cohort for time-to-treatment discontinuation (TTD) and overall survival on CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) and immune checkpoint inhibitors. APOBEC3B expression is positively correlated with adverse outcomes in estrogen receptor-positive breast cancers [22]. We utilized breast cancer samples from The Cancer Genome Atlas . Our immunohistochemistry data Mar 19, 2024 · A research team has discovered the key role that the APOBEC3A and APOBEC3B enzymes play in driving cancer mutations by modifying the DNA in tumor genomes, offering potential new targets for Nov 1, 2015 · Notably, APOBEC3B upregulation can be as high as 100-fold and this mRNA level is on par with those observed in many different cancer cell lines and tumor types including a large fraction of breast and ovarian cancers [i. However, its potential role in cervical cancer is still not fully understood. 013). Here APOBEC3B proteomics Feb 2, 2013 · A3B mRNA is up-regulated in the majority of primary breast tumors and breast cancer cell lines. Feb 6, 2013 · The DNA cytosine deaminase APOBEC3B is shown to be overexpressed and highly active in most breast cancers; deamination by APOBEC3B could serve as an endogenous, continual source of DNA damage Feb 15, 2022 · High expression of APOBEC3F was associated with improved disease-specific and overall survival in triple negative breast cancer (TNBC). 2023 Nov 30;19(11):e1011043. However, the exact molecular mechanism of APOBEC3B expression in the development of gastric cancer is still unknown. We then replicated the most promising CNV using real Dec 16, 2019 · Abstract. In Doxorubicin- and MCF-7/Eto cell lines, the expression of APOBEC3B was five-fold increased with more pronounced signal intensity compared to MCF-7/S cell line. In-depth analysis of mutation signatures in cancers has implicated both A3A and A3B in APOBEC-mediated mutagenesis ( 24 ). APOBEC3B may be a prime therapeutic target because it is non-essential, it is rarely expressed in most normal tissues, and it is a dominant-acting enzyme with an active site that Sep 21, 2023 · The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. The factors responsible for Feb 7, 2020 · Since APOBEC3B is a driver of cancer genomic diversity, we hypothesize that its over-expression may have two therapeutically opposing consequences. PMID 37270643, Free PMC Article; Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase. On the basis of these and other observations drawn from expression and deamination-based assays, APOBEC3B is often considered to be a major mutator and therapeutic target in breast and other cancer types Mar 3, 2020 · A number of studies have demonstrated that APOBEC3B mRNA expression levels are upregulated in breast cancer, which is associated with the metastasis, endocrine therapy resistance and poor prognosis of patients with estrogen receptor positive (ER+) breast cancer (22–25); however, to the best of our knowledge, the clinical relevance of the Sep 15, 2016 · We examined APOBEC3A, APOBEC3B and APOBEC3G mRNA expression levels in a panel of 15 breast cancer cell lines (five luminal, five basal and five HER2+) by quantitative PCR (Fig. Feb 6, 2013 · Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. However, its substrates in cells are not fully delineated. APOBEC3B can cause C-to-U mutations at ER target genes, to activate DNA repair. et al. 1371/journal. They report APOBEC3B can promote cytidine deamination at gene regulatory regions, with consequent repair providing a mechanism for chromatin remodelling that facilitates gene expression. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. 55 vs. Jan 4, 2022 · Among breast cancer subtypes, HER2-positive (HER2 +) breast tumors are reported to have the highest median levels of APOBEC signature enrichment . Also, A3B is introduced as the main factor contributing to mutations in Jan 6, 2017 · Purpose APOBEC3B belongs to the family of DNA-editing enzymes. Sep 30, 2016 · Connecting replication stress and APOBEC3B through ATR. A new experimental study sheds light on the inciting factors, linking APOBEC3B expression to Apr 1, 2016 · Burns et al. Feb 21, 2013 · Our data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity. 1a and Sup- Mar 30, 2023 · We and others have shown that APOBEC3B expression is relatively specific to cancer cell nucleus and impacts patient outcome in OCCC [6, 22,23,24,25]. Dec 16, 2019 · Abstract. In their knockdown experiments, increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions correlated with APOBEC3B expression. APOBEC3B (A3B) is a cellular deaminase, which is overexpressed in cancers and believed to be an important cause of cancer-associated mutations. The APOBEC3B deletion allele frequency is estimated to be 37 % in East Oct 31, 2022 · APOBEC mutagenesis underlies somatic evolution and accounts for tumor heterogeneity in several cancers, including breast cancer (BC). In other words, A3A is overexpressed in this system and A3B approximates levels observed in breast Jan 21, 2015 · APOBEC3B may be of similar importance to breast cancer, and one can already envisage developing the equivalent of a ‘sunscreen’ to inhibit APOBEC3B mutagenesis. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype of breast cancer and are associated with immunotherapy response in diverse cance … Mar 3, 2015 · Somatic mutagenesis is fundamental to the development and evolution of cancers. Dec 15, 2016 · Recent studies have identified the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B (APOBEC3B) as a source of mutations in various malignancies. They concluded that APOBEC3B could be a source of mutations. Apr 13, 2014 · A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B 5, has been associated with modestly increased risk of breast cancer 6,7,8. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. In this study, we investigate a loss-of-function mutation that selectively targets APOBEC3B, for its association with breast cancer risk. In breast cancer, expression of APOBEC3B is increased and associated with mutation load and poor outcome. show that APOBEC3B is required for the regulation of gene expression by the estrogen receptor in breast cancer cells. Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intra- and inter-tumor genomic heterogeneity and therapy resistance in, amongst others, breast cancer. APOBEC3 signature mutations in cancer are defined as C-to-T transitions and C-to-G transversions in 5’-TCW motifs (W = A or T; SBS2 and SBS13, respectively) [1, 5–10]. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of Jul 20, 2022 · APOBEC3B was reported to be the only enzyme with detectable DNA deaminase activity in cell extracts from >75% of breast cancer cell lines 14. Additionally, a recent re-analysis of public breast cancer mutation data reported that breast cancers in carriers of Jan 31, 2017 · In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. Here, A3B mRNA and protein expression levels were quantified in different cell lines and breast tumors and related to Jun 6, 2021 · High levels of APOBEC3A and APOBEC3B expression have been associated with aggressive tumor phenotypes in breast cancer. Oct 6, 2015 · Periyasamy et al. Other APOBEC3s can also mutate DNA but their clinical significance in breast cancer and its underpinnings have not been comprehensively studied. Here, we took an unbiased approach to investigate mRNA expression changes of all APOBEC3 genes during breast cancer and NSCLC evolution. In this study, we analyzed APOBEC3B mRNA expression in 305 primary breast cancers of Japanese women using quantitative reverse transcription-PCR, and investigated the relationships between the APOBEC3B mRNA expression and clinicopathological characteristics APOBEC3B expression in breast cancer David W. H Papillomaviruses (HPVs) are known to cause cancer by altering multiple signaling pathways through integration of their oncogenes into the human host genome. Expression of A3A was not detectable in any conditions May 30, 2017 · This 29. Here we show that APOBEC3H haplotype I (A3H-I) provides a likely solution to this paradox. A3B activity Jan 13, 2020 · A3B mRNA expression in 503 breast tumors in TCGA and breast cancer cell lines. Somatic mutations in cancer can give rise to unique mutant peptides that serve as immune-reactive neoantigens, allowing cytotoxic T cells to target tumor cells for elimination ( 7 ). Oct 6, 2015 · APOBEC3B is associated with poor survival in ER+ breast cancer patients. APOBEC3F is not usually a reflection of cancer cell biology in TNBC or luminal breast cancer, except for homologous recombination deficiency in TNBC. APOBEC3 mutates the cancer genome in a broad range of cancer types. Its overexpression and aberrant activation lead to unexpected clusters of mutations in the majority of cancers. Recent studies in breast cancer identified that A3B mRNA is upregulated at the DCIS stage (24,54), but these studies did not investigate the entire repertoire of APOBEC3 genes. To determine if A3B expression was correlated with response to chemotherapy treatments, we analysed two large, independent, breast May 27, 2016 · APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. PMID 37190094, Free PMC Article An evaluation of mutational signatures in breast cancer genomes from patients with the A3B deletion demonstrated an increase in APOBEC3 mutational hallmarks , which are consistent with the activity of A3A based on its distinct mutational signature including a pyrimidine in the −2 position preceding a mutated cytosine . 0 (stage 1). pgen. Jul 26, 2020 · Background Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. However, A3B-null breast tumours still have this mutational bias. Second, APOBEC3B depletion in an ER + breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. 0. In lung cancer, the loss of FHIT1 —a common genetic alteration that causes replication stress—was associated with a higher APOBEC3-induced mutation burden [ 53 ]. Mar 11, 2021 · Burns, M. Conclusions: Our study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in breast cancer patients. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines. In humans, APOBEC3B has also been reported to be significantly May 5, 2023 · Abstract. relative to controls in 28 out of 38 lines, with levels exceeding tenfold in 12 out of 38 lines (Fig. APOBEC3B controls breast cancer cell growth by promoting ER transcriptional activity. doi: 10. High APOBEC3B expression predicts worse outcomes in lung cancer and recurrence of clear cell renal cell carcinomas Mar 3, 2020 · APOBEC3B protein expression in 120 patients with breast cancer was evaluated via immunohistochemistry, using a constructed tumor microarray, and TILs were analyzed by hematoxylin and eosin staining. May 27, 2016 · Given that APOBEC3B expression is upregulated in breast tumours, and that its upregulation is associated with APOBEC-associated mutational signatures [3–5], it has been suggested that APOBEC3B may be an endogenous source of mutations in cancers, especially breast cancer. Here, A3B mRNA and protein expression levels were quantified in differen … Sep 19, 2022 · APOBEC3B is the most common member of the family, and it is involved in the development of cancer, including liver cancer , breast cancer , gastric cancer , chondrosarcoma , kidney cancer , colorectal cancer , cervical squamous cell carcinoma , lung cancer , and bladder cancer . The median mRNA levels for A3A was lower than that of A3B in the breast cancer tissues. PLoS genetics . These cell lines, T-47D (ER+) and MDA-MB-231 (ER-), differed by the status of the estrogen receptor (ER). Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable Background: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. A3B-null tumours with … Sep 5, 2022 · A3B is considered to induce mutation in breast cancer and overexpression of APOBEC3B is reported in variety of cell lines [26]. Patients and methods: RNA was isolated from 55 primary breast nature profile seen in breast cancer. [12] demonstrated that APOBEC3B mRNA is upregulated in most primary breast tumors and breast cancer cell lines. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. Nov 30, 2023 · Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates-APOBEC3A, APOBEC3B, and APOBEC3H. A3B gene expression is increased in many cancers, but its upstream dr … Nov 30, 2023 · In comparison, the A3B and A3B-E255A mRNA levels in granddaughter clones are similar to averages reported for breast cancer cell lines of the CCLE and breast tumors of the TCGA, and approximately 2-fold lower than those of BT474 and MDA-MD-453 . Cell Death Dis, 2023 Jun 3. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). Jan 7, 2021 · A 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian descent compared to European descent. Apr 8, 2024 · APOBEC3 cytidine deaminases have emerged as key drivers of mutagenesis in a wide spectrum of tumor types and are now appreciated to play a causal role in driving tumor evolution and drug resistance. In humans, APOBEC3B has also been reported to be significantly Sep 15, 2016 · Significance. Tumors that express high levels of A3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53. In this study, we analyzed APOBEC3B mRNA expression in 305 primary breast cancers of Japanese women using quantitative reverse transcription-PCR, and APOBEC3B is overexpressed in several human cancer types, including breast cancer. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3′UTR, and it is associated with an increased risk for breast cancer in Asian women. Oct 1, 2020 · First, APOBEC3B expression correlates with specific clinical outcomes indicating a role in disease progression. Mar 16, 2020 · A3B mRNA levels in the breast cancer tissues were significantly higher than in the normal breast tissues (median 0. We investigated the effect of APOBEC3B on the malignant biological behavior of Aug 31, 2017 · Expression of APOBEC3B is prevalent in several cancer types (17, 20–23). Sep 21, 2016 · Cytosine mutations within TCA/T motifs are common in cancer. Here we show A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B 5, has been associated with a modest increased risk of breast cancer 6-8. Results HER2 amplification, PTEN and NF1 somatic mutations are associated with the APOBEC3 signature It has recently been shown that HER2-enriched (HER2+) breast cancers are associated with a high burden of mutations attributable to APOBEC3B [9]. Article ADS CAS PubMed PubMed Central Google Scholar Jan 15, 2024 · Rs1014971 has also been associated with an increased cancer risk and the APOBEC3B expression in breast cancer . The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Zong C, et al. However, we found no evidence for such a Oct 7, 2016 · Second, APOBEC3B depletion in an ER + breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Mar 18, 2024 · Based in part on its expression in breast cancer-derived cell lines and tumors, one group of investigators concluded that A3B is the source of mutations in breast cancer cells 35 but subsequent Sep 30, 2016 · Kanu and colleagues focused on the association between replication stress and APOBEC3B activity in breast cancer cell lines, starting from the observation that the HER2-enriched subtype of breast cancers exhibits the greatest burden of APOBEC mutations [] and the premise that oncogene-induced replication stress exposes single-stranded DNA (ssDNA) substrate susceptible to APOBEC mutagenesis []. 5 kB deletion between exon 5 in APOBEC3A and exon 8 in APOBEC3B is linked to increased risk for breast cancer, hepatocellular carcinoma (HCC) and epithelial ovarian cancer, whereas this deletion polymorphism is not involved with clinical outcome of mammary cancer regardless of APOBEC3B mRNA levels [13, 86,87,88,89]. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for Jan 16, 2024 · Gastric cancer is a common malignant tumor with a high mortality rate. B. We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A Jun 12, 2018 · It is highly likely that a synergy between estrogen and p53 insufficiency caused by HPV E6 oncoprotein induces Apobec3B expression which leads to initiation of breast carcinogenesis, a putative mechanism of breast cancer development. Nature 494 , 366–370 (2013). Methods We performed Mar 5, 2024 · APOBEC3B coordinates R-loop to promote replication stress and sensitize cancer cells to ATR/Chk1 inhibitors. We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A Apr 26, 2018 · We found, similar to the situation in breast cancer, APOBEC3B expression is also associated with increased TP53 mutations based on two independent NSCLC genomic databases (Supplementary Figures Aug 12, 2020 · To test this hypothesis, we measured the expression of APOBEC3A (A3A) and APOBEC3B (A3B) genes in two breast cancer cell lines treated with estradiol, cisplatin or their combination. APOBEC enzymes normally function in innate immune responses, including those that target retroviruses, suggesting links between mutagenesis, immunity and viral infection in the process of cancer development Jul 17, 2018 · However, there was no association between APOBEC3B expression and prognosis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. 2a ). of breast cancers arising in women with APOBEC3B germline deletion, and that this may be of particular interest in Asian women where the germline deletion is more common. Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. Recent evidence has implicated APOBEC3B as a source of mutations in cervical, bladder, lung, head and neck, and breast cancers. A copy number variant targeting the genomic APOBEC3A-APOBEC3B locus has a significant impact on breast cancer risk, but the relative contribution of APOBEC3B is uncertain. Abnormal APOBEC3B (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B) expression increases tumor susceptibility. d. Understanding the available methods for clinical detection of these enzymes Second, APOBEC3B depletion in an ER + breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Besides, endogenous APOBEC3B is likely the Dec 15, 2020 · Chemotherapeutic drugs stimulate A3B expression in cancer cells. M. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early Oct 7, 2016 · First, APOBEC3B levels in primary estrogen receptor-positive (ER +) breast tumors inversely correlate with the clinical benefit of tamoxifen in the treatment of metastatic ER + disease. Most luminal cell lines (green) exhibited low levels of APOPEC3B mRNA expression, whereas most of the HER2+ (red) exhibited higher APOBEC3B mRNA levels (Fig. This enzyme is normally an effector protein in the innate immune response to virus infection but upregulation in these Sep 20, 2022 · APOBEC3B is the most common member of the family, and it is involved in the development of cancer, including liver cancer , breast cancer , gastric cancer , chondrosarcoma , kidney cancer , colorectal cancer , cervical squamous cell carcinoma , lung cancer , and bladder cancer . This finding was particularly notable for bladder, head and Apr 1, 2016 · In conclusion, APOBEC3B in MCF-7/S breast cancer cell lines have been expressed in a minor population (5%) of tumor cells with a very low signal intensity. Apr 8, 2024 · Over a decade ago, a germline A3A-B deletion polymorphism variant that leads to deletion of the A3B coding sequence and fusion of the A3B 3′ UTR onto A3A was reported to be associated with an increased risk of developing breast cancer, and subsequent studies have suggested increased risk of developing ovarian, prostate, and lung cancers in Mar 28, 2023 · In breast cancer, for example, PTEN depletion and HER2 amplification have been shown to induce replication stress and increase APOBEC3B activity in vitro . An A3AB fusion gene resulting from a deletion in the APOBEC3A-APOBEC3B locus encodes A3A and associates with increased risk for breast and ovarian a total of 38 independent breast cancer cell lines. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated. A clear negative link between ER and APOBEC3B expression suggests that estrogens down-regulate this gene. 1011043 Oct 15, 2021 · In line with this, APOBEC3B gene expression in breast cancer is elevated in tumors with adverse pathological features and worse clinical outcome [11,16]. Our IHC data confirmed overexpression Sep 24, 2015 · Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A Carpenter MA, Temiz NA, Ibrahim MA, Jarvis MC, Brown MR, Argyris PP et al. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by May 30, 2017 · APOBEC3B, a DNA cytosine deaminase, is overexpressed in a wide spectrum of human cancers. Apr 18, 2023 · APOBEC3B (A3B) is aberrantly overexpressed in a subset of breast cancers, where it associates with advanced disease, poor prognosis, and treatment resistance, yet the causes of A3B dysregulation in breast cancer remain unclear. Sep 29, 2022 · Increasing research has shown that APOBEC3B may be a predominant mutagenic factor influencing the occurrence and evolution of various cancers such as breast cancer , gastric cancer , chondrosarcoma , hepatocellular carcinoma , and so on. Cells, 2023 Apr 18. cb ui ca zi ew fg op hu kl za