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

Male breast cancer is a relatively rare disease that represents about 1% of all male malignancies. Its genetic basis has received little attention. Allelic imbalance, reflected by change in microsatellite repeat number (MSI) or loss of heterozygosity (LOH), is thought to play an important role in carcinogenesis. In this study we have examined DNA extracted from paraffin tissue from 15 patients treated for male breast cancer, for evidence of such abnormalities, at 20 different loci across the genome. Polymerase chain reaction amplified products of normal and tumor DNA pairs were compared by electrophoresis on Spreadex gels. MSI was detected in 5 patients; at a single site in 2 cases and at 3, 7 and 9 sites in another 3 cases. LOH was seen in 8 cases (53%); at more than one site in 4 of these. Two patients had allelic variation at 56 and 62% of assessable sites. The most unstable loci were D2S441 (33%) and D13S325 (27%). These observations indicate that replication errors and allelic loss characterise male breast cancer tissue in much the same way as they do in women. More studies will be needed to establish whether these are random lesions or whether there are specifically affected sites that occur in both male and female breast cancer.
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PMID:Loss of heterozygosity and microsatellite instability in male breast cancer. 1183 19

HER2-positive status is the sole criterion for identifying patients with breast cancer for Herceptin therapy, which has known efficacy in women with metastatic breast cancer (MBC). Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), which measure the HER2 protein and gene, respectively, are currently the most widely used HER2 tests in the clinical setting. However, results from these assays are influenced by many variables including choice of antibody or probe, methodology, level of user experience and interlaboratory variability. Although there is no widespread standard testing algorithm, the importance of HER2 in clinical practice demands accurate and reproducible tests. Polymerase chain reaction (PCR) and chromogenic in-situ hybridization (CISH) represent upcoming methods for assessing HER2 gene amplification. Enzyme-linked immunosorption assay (ELISA), a semi-automated technique that can be used to measure the level of the HER2 extracellular domain (ECD) in serum, may also prove useful. While such technologies show great promise, they will at least have to be validated against IHC or FISH before being accepted into routine clinical practice.
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PMID:Emerging technologies for HER2 testing. 1242 53

Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells harvested from tumor bearing mice demonstrated as few as 10(2) injected tumor cells produced BM micrometastases at 4 weeks postinjection. Small foci of tumor cells were identified in the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases, detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance gene (neo) were also transduced into Clone 66 cells (Cl66-GFPneo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis of organ specificity of metastasis.
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PMID:A murine model of bone marrow micrometastasis in breast cancer. 1249 85

During the last few decades a substantial amount of evidence has accumulated proving that the abrogation of the normal p53 pathway is a critical step in the initiation and progression of tumors. Decoding the genetic mechanisms involved in carcinogenesis requires screening for consistent genetic tumor alterations, including those concerning the p53 gene. Thus, practical, efficient, and inexpensive techniques for accurate determination of p53 mutational status are needed. Polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis is considered to be a useful tool to investigate the role of the p53 gene in the development and progression of human cancers. The sensitivity of the method can be increased considerably by varying the experimental conditions. Here we demonstrate a scheme of PCR-SSCP optimization for detection of p53 gene mutations of patients with various cancers. Optimal conditions for PCRSSCP of p53 exons 4-9 are reported. Such PCR-SSCP optimization could allow an increase in the sensitivity and reproducibility of the technique and facilitates screening of large series of patients to assess the clinical significance of p53 mutations in human cancers. Using the optimized PCR-SSCP analysis we screened Bulgarian patients with invasive breast cancer for p53 gene mutations and registered a 33.33% frequency of mutations. To date, there are no data concerning the p53 status of Bulgarian breast cancer patients. Screening for p53 gene mutations enables an accurate and routine determination of the p53 status of patients with cancer and may be applied in clinical oncology to cancer diagnosis, prediction of prognosis and response to treatment.
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PMID:Optimized polymerase chain reaction-based single-strand conformation polymorphism analysis of p53 gene applied to Bulgarian patients with invasive breast cancer. 1464 33

The aim of our study was to determine whether or not the tyrosine kinase receptor, HER2 (also known as ErbB2/Her2/neu), is overexpressed in human osteosarcomas (OS). We studied 15 biopsy and 18 resection specimens at the mRNA and protein levels. HER2 status in the OS specimens was assessed by immunohistochemistry (IHC) and quantitative Real-Time Polymerase chain reaction (PCR). In moderately immunopositive cases fluorescent in situ hybridisation (FISH) analysis was used in order to identify any possible gene amplification. 27 samples were evaluable for IHC and only 1 case showed a moderately positive membrane staining. The remaining samples showed no staining or focal cytoplasmic staining (2 samples). In the moderately positive case, FISH analysis showed no HER-2 gene amplification. There was also no overexpression of HER2 mRNA suggesting this sample was a false-positive immunostain. HER2 mRNA expression was present in all samples at a similar level to that in the breast cancer cell line, MCF7, which does not overexpress HER2 and was used as a negative control. In conclusion, this study shows that HER2 mRNA or membranous HER2 protein overexpression is absent in human OS. We noted various inconsistencies in previous published studies, with regard to methodology and the interpretation of the results based on poor methodology. We therefore conclude that the positive data with regard to HER2 overexpression reported in these previous studies is not reliable. Our results suggest that the monoclonal antibody trastuzumab (Herceptin(R)), directed against the HER2-receptor, is not likely to be an effective therapeutic agent in OS.
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PMID:Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas. 1509 66

We aimed at determining whether any association exists between genetic polymorphisms in epoxide hydrolase (EPHX1), NADPH-quinone oxidoreductase (NQO1), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to breast cancer. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in EPHX1 (exons 3 and 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case-control study comprised of 238 patients with breast cancer and 313 healthy individuals. The distribution of genotypes in exon 6 of NQO1 was significantly different between the control group and breast cancer cases. Age-adjusted odds ratio (OR) for variant genotype NQO1*2/*2 was 3.68 (confidence interval (CI) = 1.41-9.62, P = 0.008). Association of GSTP1*2/*2 genotype as well as that of low EPHX1 activity deduced by combinations of genotypes in exons 3 and 4 with breast cancer was suggestive, but nonsignificant. Individuals simultaneously lacking GSTM1 and carrying at least one GSTP1 variant allele were at significantly higher risk of breast cancer (OR = 2.03, CI = 1.18-3.50, P = 0.010). Combinations of either GSTM1null or GSTP1*2 with low activity of EPHX1 presented significant risk of breast cancer (OR = 1.88, CI = 1.00-3.52, P = 0.049 and OR = 2.40, CI = 1.15-5.00, P = 0.019, respectively) as well. In conclusion, the results suggest that genetic polymorphisms in biotransformation enzymes may play a significant role in the development of breast cancer.
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PMID:Breast cancer: role of polymorphisms in biotransformation enzymes. 1528 Sep 3

The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor suppressor gene, is induced in cells treated with retinoids. RIG1 has been shown to express ubiquitously and the increased expression of this gene appears to suppress cell proliferation. Recent studies also demonstrated that this gene may play an important role in cell differentiation and the progression of cancer. In spite of the remarkable regulatory role of this protein, the molecular mechanism of RIG1 expression induced by retinoids remains to be clarified. The present study was designed to study the molecular mechanism underlying the all-trans retinoic acid (atRA)-mediated induction of RIG1 gene expression. Polymerase chain reaction was used to generate a total of 10 luciferase constructs that contain various fragments of the RIG1 5'-genomic region. These constructs were then transfected into human gastric cancer SC-M1 and breast cancer T47D cells for transactivation analysis. atRA exhibited a significant induction in luciferase activity only through the -4910/-5509 fragment of the 5'-genomic region of RIG1 gene relative to the translation initiation site. Further analysis of this promoter fragment indicated that the primary atRA response region is located in between -5048 and -5403 of the RIG1 gene. Within this region, a direct repeat sequence with five nucleotide spacing, 5'-TGACCTctattTGCCCT-3' (DR5, -5243/-5259), and an inverted repeat sequence with six nucleotide spacing, 5'-AGGCCAtggtaaTGGCCT-3' (IR6, -5323/-5340), were identified. Deletion and mutation of the DR5, but not the IR6 element, abolished the atRA-mediated activity. Electrophoretic mobility shift assays with nuclear extract from atRA-treated cells indicated the binding of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers specifically to this response element. In addition to the functional DR5, the region contains many other potential sequence elements that are required to maximize the atRA-mediated induction. Taken together, we have identified and characterized the functional atRA response element that is responsible for the atRA-mediated induction of RIG1 gene.
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PMID:Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter. 1585 Aug 6

The structure of the Gene 33 protein suggests that it plays a role in intracellular signaling and Gene 33 is induced by many mitogenic and stressful stimuli. Previously, we found that Gene 33 expression is significantly induced by retinoic acid (RA), insulin and synergistically by both in a liver-derived cell line. In the present study, we investigated the basal expression and regulation of Gene 33 in multiple human breast cancer cell lines. These cell lines expressed different levels of Gene 33 protein, but Gene 33 protein was not regulated by RA or insulin, either alone, or in combination. However, epidermal growth factor (EGF) induced Gene 33 expression in SK-BR-3 cells and this induction was inhibited by co-treatment with RA. There was a strong correlation between endogenous basal Gene 33 expression and doubling time. Exogenous expression of Gene 33 in MCF-7 cells did not affect cell cycle distribution, but inhibited apoptosis and specifically increased the level of Poly(ADP-ribose) Polymerase (PARP-1) protein. This suggests that Gene 33 promotes breast cancer cell growth by an anti-apoptotic rather than a mitogenic effect, possibly involving up-regulation of PARP-1.
Breast Cancer Res Treat 2005 Jun
PMID:Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression. 1595 54

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.
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PMID:Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis. 1604 4

To shed light on the relationships between over-expression of anti-apoptotic proteins, genomic instability, and the metastatic ability of breast cancer cells, we analyzed genetic changes in tumors and metastases by orthotopically injecting MDA-MB 435 cells transfected with anti-apoptotic genes Bcl-xL or Bcl-2 into nude mice. Tumors and metastasis variants were extracted by primary culture from breast, bone, lung, and lymph node from mice with 435/Bcl-xL, 435/Bcl-2, and 435/Neo tumors. Using the Arbitrarily Primed Polymerase Chain Reaction (AP-PCR), which permits the detection of allelic imbalances, we generated four different fingerprints utilizing four primers. We found that the genetic damage fraction (GDF) increased in 435/Bcl-2 (GDF=0.55) and 435/Bcl-xL cells (GDF=0.34), in regard to 435/Neo control cells (GDF=0.29), indicating that non-random genetic alterations occurred in cells secondary to Bcl-2 or Bcl-xL over-expression. Anti-apoptotic proteins render breast cancer cells susceptible to the in vivo acquisition of highly tumorigenic (Kruskal-Wallis, P=0.019) and metastatic (Kruskal-Wallis, P=0.004) activity. We therefore propose that genetic instability is a molecular mechanism favored by anti-apoptotic proteins involved in the selection of highly metastatic cells during tumorigenesis, a pathogenic event favoring the expansion of metastasis.
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PMID:Anti-apoptotic proteins induce non-random genetic alterations that result in selecting breast cancer metastatic cells. 1617 Jun 66


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