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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We aimed at determining whether any association exists between six single nucleotide polymorphisms in breast cancer associated gene (BRCA1) and the risk of breast cancer. We constructed haplotypes and analyzed their importance as well. Clinico-pathological characteristics of breast cancer patients were included in the study to evaluate the prognostic impact of BRCA1 polymorphisms and haplotypes. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in codons 356, 871, 1038, 1183, 1436, and 1613 of BRCA1 in a group of 306 incident breast cancer patients and 313 unaffected controls of Czech origin. Statistical analyses revealed that the BRCA1 Arg356 allele may play a protective role in breast cancer (age-adjusted OR = 0.61, CI = 0.39-0.94, p = 0.026). We also observed a significant correlation between polymorphism Gln356Arg and stage (p = 0.026) in premenopausal cases suggesting that carriers of the wild Gln356Gln allele are at significantly higher risk of advanced disease. The most common haplotypes of BRCA1 did not play a significant role in breast cancer either as risk factors or as prognostic factors. The study on rare BRCA1 haplotypes however should be repeated using larger groups. In conclusion, the BRCA1-Gln356 allele presents risk factor in the onset and progression of breast cancer in Czech population and its use as a possible screening tool should be considered.
Breast Cancer Res Treat 2007 Jun
PMID:Role of single nucleotide polymorphisms and haplotypes in BRCA1 in breast cancer: Czech case-control study. 1703 64

This study was carried out to evaluate the loss of heterozygosity (LOH) in the 8q12-q24.1 chromosomal region, containing RAD54B gene in breast cancer. Polymorphic markers D8S539 and D8S543 were used. For alleles frequency estimation 100 primary breast cancers were tested. DNA was isolated from paraffin-embedded tissues and their matched blood samples. Polymerase chain reaction amplified products of normal and tumor DNA pairs were compared in ABI PRISM 377 DNA sequencer. In analyzed cases LOH was found in 1% and 2% of informative cases for microsatellite markers D8S539 and D8S543, respectively. This date indicate, that LOH isn't predictive for breast cancer.
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PMID:Loss of heterozygosity in the RAD54B region is not predictive for breast carcinomas. 1758 36

Breast cancer is one of the most frequently diagnosed cancers in women in France, but its aetiology remains unknown. Viruses including Epstein-Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been detected in benign breast tissues and breast tumours and are considered to be involved in the aetiology of breast cancer. The aim of this study was to determine the prevalence of high-risk oncogenic HPVs in breast carcinoma from French patients. Fifty unselected DNA samples extracted from invasive breast carcinoma tissues were analysed. Polymerase chain reaction (PCR) was performed to amplify both consensus GP5+/GP6+HPV sequences and specific sequences for HPV types 16, 18, 33, 45 and 6-11. No HPV-DNA sequences were detected in our series of 50 samples. These data argue against the role of oncogenic HPV in the pathogenesis of breast cancer.
Breast Cancer Res Treat 2008 May
PMID:No evidence of human papillomavirus DNA sequences in invasive breast carcinoma. 1762 90

We previously showed that COUP-TFI interacts with the Estrogen Receptor alpha (ER alpha) to recruit Extracellular signal Regulated Kinases (ERKs) in an Estradiol (E2)-independent manner, resulting in an enhancement of ER alpha transcriptional activity. However, the involvement of COUP-TFI in physiologically relevant functions of ER alpha, such as the mitogenic activity that E2 has on breast cancer cells, remains poorly understood. Here, we first showed that the amounts of COUP-TFI protein are higher in dedifferentiated mammary cell lines (MDA-MB-231) and tumor breast cells as compared to the differentiated MCF-7 cell line and normal breast cells. To evaluate the functional relevance of the COUP-TFI/ER alpha interplay in mammary cells, we generated MCF-7 cells that stably over-express COUP-TFI. We found that the over-expression of COUP-TFI enhances motility and invasiveness of MCF-7 cells. COUP-TFI also promotes the proliferation of MCF-7 cells through ER alpha-dependent mechanisms that target cell cycle progression and cell survival. To further investigate the mechanisms underlying these effects of COUP-TFI, we evaluated the expression of known E2-target genes in breast cancer, and found that COUP-TFI differentially regulated genes involved in cell proliferation, apoptosis, and migration/invasion. Notably, Cathepsin D (CTSD) transcript and protein levels were significantly higher in presence and absence of E2 in MCF-7 over-expressing COUP-TFI. Chromatin Immunoprecipitation assays showed that ER alpha, phospho-RNA Polymerase II, as well as p68 RNA Helicase, a phospho-Serine 118 dependent co-activator of ER alpha, were preferentially recruited onto the CTSD gene proximal promoter in COUP-TFI over-expressing cells. These results suggest that COUP-TFI selectively regulates the expression of endogenous E2-target genes and consequently modifies ER alpha positive mammary cells response to E2.
Breast Cancer Res Treat 2008 Jul
PMID:COUP-TFI modulates estrogen signaling and influences proliferation, survival and migration of breast cancer cells. 1767 91

In this study, we examined the role of sphingosine-1-phosphate (S1P) in regulating the transcription of the liver receptor homologue-1 (LRH-1) in breast cancer cells. We show that S1P induces LRH-1 mRNA expression in MCF-7 cells in a prostaglandin E2 (PGE2)-dependent manner. Both S1P and PGE2 stimulate the recruitment of LRH-1, cAMP response element binding protein (CREB), CCAAT/enhancer binding proteins (C/EBP), and RNA Polymerase II (Pol II) to the LRH-1 promoter, as well as increase acetylation of histone H3 in this region of chromatin. S1P and PGE2 promote the direct interaction of CREB and LRH-1, which is potentiated by C/EBPdelta and the coactivators CREB-binding protein (CBP), and steroid receptor coactivator-3 (SRC-3). CREB and LRH-1 synergistically increase LRH-1 transcription, suggesting an integral role for LRH-1 in regulating the transcription of its own gene.
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PMID:Sphingosine-1-phosphate regulates the expression of the liver receptor homologue-1. 1819 Oct 17

Human papillomavirus (HPV) is considered the aetiological agent for cervical cancer. Several reports have addressed a relationship with HPV and breast cancer, as different HPVs have been identified. The purpose of this study was to detect HPV DNA in 67 breast cancer patients and 40 non-malignant disease breast tissues by means of Polymerase Chain Reaction with consensus primers. The frequency of HPV in the cases group were 4.4% (3/67) and no positive samples among the reference group were identified. From the 3 positive samples, HPV types 16, 18 and 33 were identified by restriction patterns and direct sequencing. The high diversity among detection in the related studies shows that population genomic heterogeneity plays an important role in the disease. The low frequency detected in the present study suggests that HPV does not play an important role in breast cancer.
Breast Cancer Res Treat 2009 Mar
PMID:Low frequency of human papillomavirus DNA in breast cancer tissue. 1837 73

Although Smad signalling is known to play a tumour suppressor role, it has been shown to play a prometastatic function also in breast cancer and melanoma metastasis to bone. In contrast, mutation or reduced level of Smad4 in colorectal cancer is directly correlated to poor survival and increased metastasis. However, the functional role of Smad signalling in metastasis of colorectal cancer has not been elucidated. We previously reported that overexpression of Smad7 in colon adenocarcinoma (FET) cells induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Here, we have observed that abrogation of Smad signalling by Smad7 induces liver metastasis in a splenic injection model. Polymerase chain reaction with genomic DNA from liver metastases indicates that cells expressing Smad7 migrated to the liver. Increased expression of TGF-beta type II receptor in liver metastases is associated with phosphorylation and nuclear accumulation of Smad2. Immunohistochemical analyses have suggested poorly differentiated spindle cell morphology and higher cell proliferation in Smad7-induced liver metastases. Interestingly, we have observed increased expression and junctional staining of Claudin-1, Claudin-4 and E-cadherin in liver metastases. Therefore, this report demonstrates, for the first time, that blockade of TGF-beta/Smad pathway in colon cancer cells induces metastasis, thus supporting an important role of Smad signalling in inhibiting colon cancer metastasis.
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PMID:Smad7 induces hepatic metastasis in colorectal cancer. 1878 Nov 53

Variants in several genes are known to confer increased susceptibility to breast cancer, but the frequencies of these mutations in the population are very rare and different between race or ethnic groups. Genetic variation in trinucleotide repeat containing 9 (TNRC9) and the hypothetical gene LOC643714 (TNRC9/LOC643714) is a newly described risk factor for breast cancer. Here, we investigated the association among the three single nucleotide polymorphisms (SNPs) in TNRC9/LOC643714 and breast cancer risk and clinico-pathological parameters in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. Polymerase chain reaction-ligation detection reaction was used to genotype 321 breast cancer cases and 330 controls. In addition, the representative polymerase chain reaction products were subjected to direct DNA sequencing to confirm the accuracy of this method. The odds ratios and 95% confidence intervals were calculated by an unconditional logistic regression model. There was no significant association between the risk of breast cancer and three SNPs of TNRC9/LOC643714 gene polymorphisms and their haplotypes. No significant correlation was found between the TNRC9/LOC643714 polymorphisms and age at diagnosis, lymph node metastases, estrogen receptor status, or progesterone receptor status, respectively. None of these three SNPs of TNRC9/LOC643714 gene is associated with individual susceptibility to breast cancer in Chinese women.
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PMID:TNRC9/LOC643714 polymorphisms are not associated with breast cancer risk in Chinese women. 1939 14

Decreased mitochondrial oxidative phosphorylation (OXPHOS) is one of the hallmarks of cancer. To date, the identity of nuclear gene(s) responsible for decreased OXPHOS in tumors remains unknown. It is also unclear whether mutations in nuclear gene(s) responsible for decreased OXPHOS affect tumorigenesis. Polymerase-gamma (POLG) is the only DNA polymerase known to function in human mitochondria. Mutations in POLG are known to cause mitochondrial DNA (mtDNA) depletion and decreased OXPHOS, resulting in mtDNA depletion syndrome in humans. We therefore sequenced all coding exons (2-23) and flanking intron/splice junctions of POLG in breast tumors. We found that the POLG gene was mutated in 63% of breast tumors. We identified a total of 17 mutations across the POLG gene. Mutations were found in all three domains of the POLG protein, including T251I (the exonuclease domain), P587L (the linker region) and E1143G (the polymerase domain). We identified two novel mutations that include one silent (A703A) and one missense (R628Q) mutation in the evolutionarily conserved POLG linker region. In addition, we identified three novel mutations in the intronic region. Our study also revealed that mtDNA was depleted in breast tumors. Consistently, mutant POLG, when expressed in breast cancer cells, induced a depletion of mtDNA, decreased mitochondrial activity, decreased mitochondrial membrane potential, increased levels of reactive oxygen species and increased Matrigel invasion. Together, our study provides the first comprehensive analysis of the POLG gene mutation in human cancer and suggests a function for POLG (1) in decreased OXPHOS in cancers and (2) in promoting tumorigenicity.
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PMID:Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. 1962 38

The purpose of this study is to investigate EZH2 in a large series of breast cancer patients for its prognostic and predictive value, and to evaluate its functional role in treatment response in vitro. EZH2 levels were measured using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in primary breast cancer specimens and related to clinicopathologic factors and disease outcome. EZH2 expression was downregulated with siRNAs in MCF7, to assess expression alterations of putative EZH2 downstream genes and to determine cell numbers after treatment with the anti-estrogen ICI 164384. In 688 lymph node-negative patients who did not receive adjuvant systemic therapy, EZH2 was not significantly correlated with metastasis-free survival (MFS). In 278 patients with advanced disease treated with first-line tamoxifen monotherapy, the tertile with highest EZH2 levels was associated with the lowest clinical benefit (OR = 0.48; P = 0.02) and with a shorter progression-free survival (PFS) in both univariate (HR = 1.80; P < 0.001) and multivariate analysis, including traditional factors (HR = 1.61; P = 0.004). In vitro, EZH2 silencing in MCF7 caused a 38% decrease in cell numbers (P < 0.001) whereas ICI 164384 treatment resulted in a 25% decrease (P < 0.001) compared to controls. Combining EZH2 silencing with ICI treatment reduced cell numbers with 67% (P < 0.001) compared to control conditions. EZH2 downregulation was associated with an almost two-fold upregulation of the estrogen receptor alpha (ER) (P = 0.001). In conclusion, EZH2 has no prognostic value in breast cancer. High levels of EZH2 are associated with poor outcome to tamoxifen therapy in advanced breast cancer. Downregulated EZH2 leads to upregulation of the ER and better response to anti-estrogens.
Breast Cancer Res Treat 2011 Jan
PMID:Decreased expression of EZH2 is associated with upregulation of ER and favorable outcome to tamoxifen in advanced breast cancer. 2030 27


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