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

Recent evidence obtained by in situ hybridization indicates that chromosomal region 17q is often lost in prostate tumors. To substantiate the presence of tumor suppressor genes in this chromosomal region, normal human 17q tagged with a neomycin resistance gene was transferred into a human prostate cancer cell line, PPC-1, by microcell-mediated chromosome transfer. Two hybrid clones were obtained, both of which showed decreased tumorigenicity in athymic nude mice and decreased efficiency of colony formation in soft agar with respect to PPC-1. When microcells were irradiated prior to transfer of chromosomal region 17q to determine which subchromosomal regions carry the potential tumor suppressor gene(s), 10 hybrid clones were obtained, including 6 fully malignant and 4 suppressed clones. Analysis of polymorphic loci on 17q in the series of hybrid clones suggested that a tumor suppressor gene associated with prostate cancer was located in a region no more than 28 cM long at 17q12-q22, which includes the BRCA1 gene involved in hereditary breast cancer.
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PMID:Suppression of malignant phenotype in a human prostate cancer cell line by fragments of normal chromosomal region 17q. 761 77

Loss of heterozygosity (LOH) on chromosome 17 is a frequent genetic alteration in breast cancer. To assess whether the location of potential tumor suppressor genes is compatible with the LOH pattern in individual tumors, we analyzed allele loss on chromosome 17 in 121 invasive ductal breast carcinomas and 16 benign breast tumors with 14 polymorphic microsatellite markers (4 on 17p and 10 on 17q). Fluorescent polymerase chain reaction (PCR) for typing microsatellites coupled with DNA fragment analysis in an automated DNA sequencer was applied. Frequencies of LOH varied from 29.4% (D17S1322) to 57.4% (TP53-Alu). No LOH could be detected in benign breast tumors. In 54 tumors the deletion patterns were consistent with the complete loss of 17p (n = 28), 17q (n = 9) or the whole chromosome 17 (n = 17). Five smallest regions of overlap (SROs) were identified in tumors with interstial deletion patterns. On 17p, two foci were detected affecting the TP53 locus and the hypermethylated in cancer I (HICI) region (17p13.3). On 17q, SRO1 was localized between markers THRAI and D17S855, centromeric to the breast/ovarian cancer gene BRCAI; SRO2 was flanked by markers AFM234 and NMEI, and SRO3 was centered between markers MPO and GH. Associations between LOH and histopathological characteristics were determined. Significant correlations were found between higher grade and loss of the TP53 gene (marker TP53, P = 0.019), loss of the BRCAI region (P < 0.009), LOH of marker AFM155 (P = 0.003) and marker NMEI (P = 0.026). For positive estrogen receptor status, only LOH of the THRAI marker correlated significantly, whereas highly significant correlations were determined between positive progesterone receptor and markers centromeric to the BRCAI region D17S250 (P = 0.00002), THRAI (P = 0.0006), and the intragenic BRCAI markers [D17S1322 (P = 0.021), D17S855 (P = 0.029)]. Results presented in this study identify five independent regions of chromosome 17 which are likely to contain potential tumor suppressor genes involved in the carcinogenesis of sporadic breast cancer.
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PMID:Patterns of allelic loss on chromosome 17 in sporadic breast carcinomas detected by fluorescent-labeled microsatellite analysis. 907 71

A new approach is applied in the mapping of tumor suppressor genes: analysis of loss of heterozygosity (LOH) in concordant tumors of monozygotic and dizygotic twins. The method relies on recognition of genome locations undergoing loss in both twins in a high proportion of the set of all twin pairs examined. The method effectively pinpoints, and excludes, the loci of potential tumor suppressor genes. With the help of a high density linkage map any such candidates can be placed within a narrow region of a chromosome arm and perhaps matched with known genes. The analysis of the Swedish Twin Registry has shown a clear genetic component for breast cancer. We have identified mono- and dizygotic twins concordant for breast cancer and collected the pathology specimens. Tumor and normal tissue was microdissected and microsatellite analysis carried out to test for allelic loss (LOH) in entirely new and putative chromosomal loci in this cancer. It can be calculated that using only six pairs of informative monozygotic twins, a locus can be incriminated with a high probability. Using increasingly dense markers and search for homozygous deletions, it should be possible to map one or more candidates for breast cancer.
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PMID:Use of twins in search for tumor suppressor genes. 932 48

Loss of heterozygosity involving the long arm of chromosome 16 is a frequent event seen in a number of human carcinomas, including breast, prostate, hepatocellular, and ovarian cancers. A region found to be commonly deleted in breast and prostate carcinomas is located at 16q24.3, which suggests the presence of a tumor suppressor gene that may be altered in these two malignancies. A detailed physical and transcription map of this region that includes the loci defining the smallest region of deletion has been constructed. This report describes the characterization of a transcript located in this region, the growth arrest-specific 11 (GAS11) gene, which was viewed as a potential tumor suppressor gene due to the expression of its mouse homolog specifically during growth arrest. The gene consists of 11 exons spanning approximately 25 kb. Northern blot analysis identified two ubiquitously expressed mRNAs of 3.4 and 1.8 kb produced by the use of alternative polyadenylation sites. Another gene, C16orf3 (chromosome 16 open reading frame 3), was found to lie within intron 2 of GAS11. This gene appears intronless, is transcribed in the orientation opposite to that of GAS11, and is expressed at low levels. These genes were examined for mutations in breast tumor DNA, and both were excluded as tumor suppressor genes involved in breast cancer.
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PMID:Characterization and screening for mutations of the growth arrest-specific 11 (GAS11) and C16orf3 genes at 16q24.3 in breast cancer. 979 Jul 51

This review summarizes the cytogenetic information on benign breast lesions of various histologies, i.e., fibrocystic lesions from women with and without a known hereditary predisposition to breast cancer, fibroadenomas, phyllodes tumors, and papillomas, and relate the chromosomal features with those in breast carcinoma. In general, the frequency of chromosome abnormalities is lower in benign lesions than in breast cancer, and seems to correlate with the histologic features of the tissue, and the corresponding risk of developing invasive mammary carcinoma; aberrations are more common in proliferative than in nonproliferative lesions. The karyotypes are generally less complex than those detected in invasive carcinoma, and more often involve balanced rearrangements. No lesion-specific aberration has so far been detected; on the contrary, changes repeatedly encountered in breast cancer samples can be found in benign lesions as well, e.g., gain of 1q, interstitial deletion of 3p, and trisomies 7, 18, and 20. Especially intriguing is the prevalence of rearrangements of the short arm of chromosome 3, with the minimally deleted bands 3p13-14, in proliferative lesions from prophylactic mastectomies in breast cancer families. The potential tumor suppressor gene(s) in this region remains, however, to be identified.
Breast Cancer Res Treat 1998 Sep
PMID:Cytogenetics of benign breast lesions. 987 25

In a search for candidate tumor suppressor genes within a 650-kb common region of loss of heterozygosity (LOH) at 16q24.3 in breast cancer tissues, a 2.6-kb cDNA, named copine VII (CPNE7), was characterized. The gene is 2654 bp and codes for a 633-residue protein with high homology to the other members of the copine family, such as copine I, copine III, and N-copine. The predicted amino acid sequence contains two copies of a C2 domain in the N-terminus. Since these domains have been found in several membrane-binding proteins involved in different intracellular processes, copine VII was viewed as a potential tumor suppressor gene. Mutation analysis was carried out by single-strand conformation polymorphism analysis of 18 breast tumor tissue samples with ascertained LOH on chromosome 16q24.3. Since only two polymorphisms were identified, no evidence was found to indicate that copine VII is the tumor suppressor gene at 16q24.3 involved in breast cancer.
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PMID:Characterization of copine VII, a new member of the copine family, and its exclusion as a candidate in sporadic breast cancers with loss of heterozygosity at 16q24.3. 1053 7

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.
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PMID:PANORAMA: an integrated Web-based sequence analysis tool and its role in gene discovery. 1116 80

Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear. In 25 (28%) of the 90 paired samples of human breast cancer and the matched, adjacent non-cancerous tissues examined here, reduced mRNA expression of Syk in the breast cancer tissues was observed by real-time quantitative reverse transcription-polymerase chain reaction. Eight (32%) of the 25 cases showing reduced Syk mRNA expression demonstrated distant metastasis of breast cancer, while only 4 (6%) of the 65 cases who did not show reduced Syk expression had distant metastasis. Kaplan-Meier curves demonstrated that patients with reduced Syk expression were at significantly increased risk for distant metastasis (P=0.0003). Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.
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PMID:Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer. 1244 83

We have characterized previously the nuclear matrix protein/scaffold attachment factor (SAFB) as an estrogen receptor corepressor and as a potential tumor suppressor gene in breast cancer. A search of the human genome for other potential SAFB family members revealed that KIAA00138 (now designated as SAFB2) has high homology to SAFB (now designated as SAFB1). SAFB1 and SAFB2 are mapped adjacent to each other on chromosome 19p13.3 and are arranged in a bidirectional divergent configuration (head to head), being separated by a short (<500 bp) GC-rich intergenic region that can function as a bidirectional promoter. SAFB1 and SAFB2 share common functions but also have unique properties. As shown previously for SAFB1, SAFB2 functions as an estrogen receptor corepressor, and its overexpression results in inhibition of proliferation. SAFB1 and SAFB2 interact directly through a C-terminal domain, resulting in additive repression activity. They are coexpressed in a number of tissues, but unlike SAFB1, which is exclusively nuclear, SAFB2 is found in the cytoplasm as well as the nucleus. Consistent with its cytoplasmic localization, we detected an interaction between SAFB2 and vinexin, a protein involved in linking signaling to the cytoskeleton. Our findings suggest that evolutionary duplication of the SAFB gene has allowed it to retain crucial functions, but also to gain novel functions in the cytoplasm and/or nucleus.
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PMID:SAFB2, a new scaffold attachment factor homolog and estrogen receptor corepressor. 1266 Feb 41

Prohibitin, a potential tumor suppressor protein, has been shown to inhibit cell proliferation and repress E2F transcriptional activity. Though prohibitin has potent transcriptional functions in the nucleus, a mitochondrial role for prohibitin has also been proposed. Here we show that prohibitin is predominantly nuclear in two breast cancer cell lines where it co-localizes with E2F1 and p53. Upon apoptotic stimulation by camptothecin, prohibitin is exported to perinuclear regions where it localizes to mitochondria. The data presented here also show that prohibitin is capable of physically interacting with p53 in vivo and in vitro. Prohibitin was found to enhance p53-mediated transcriptional activity and cotransfection of an antisense prohibitin construct reduces p53-mediated transcriptional activation. Prohibitin appears to induce p53-mediated transcription by enhancing its recruitment to promoters, as detected by chromatin immunoprecipitation assays. These results suggest that prohibitin is capable of modulating Rb/E2F as well as p53 regulatory pathways.
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PMID:Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. 1450 Jul 29


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