Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genomic alterations of c-myc (amplification, rearrangements and hypomethylation) were investigated in 30 breast carcinomas and 20 cervix carcinomas. In breast carcinomas c-myc alterations were compared with overexpression of the c-erbB2 protooncogene and the proliferation marker Ki-67. Alterations of c-myc were found in 50% of the breast carcinomas and in 25% of the cervix carcinomas. In 23% of the breast carcinomas c-erbB2 overexpression was associated with c-myc alterations. In 17% of the cases there was overexpression of c-erbB2 without detectable alterations of c-myc. Hence, in 67% of breast cancers alterations of c-myc and/or c-erbB2 have been found, while in 81% of the samples Ki-67 expression was increased. The results suggest that the study of c-myc alterations provides an important complement to that of other prognostic indicators of breast cancer such as c-erbB2 expression.
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PMID:Genomic alterations of the c-myc protooncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas. 168 73

The effects of cell surface sugar chains combined with certain gene amplifications of breast cancers on the prognosis of patients were studied and the relationships between the sugar chains of cancer cells and amplifications of the proto-oncogenes c-myc, int-2 and c-erb B-2, evaluated. One hundred and fifty three human breast carcinoma tissues were investigated by an immunohistochemical technique using the avidinbiotin-peroxidase method with 1 lectin (HPA; Helix Pomatia) and 4 monoclonal antibodies (B-72-3, St-439, anti-Tn and anti-T). The positive rates of HPA, St-439, B-72-3, anti-Tn and anti-T were 43 per cent (63/153), 52 per cent (80/153), 53 per cent (81/153), 64 per cent (98/153) and 89 per cent (136/153), respectively. Patients whose cancers had positive HPA staining were found to have a lower survival rate than those with negative HPA staining (p less than 0.05), whereas those whose cancers had positive St-439 staining showed a better prognosis than those with negative St-439 staining (p less than 0.01). The positive rate of HPA was related to the gene amplification of c-myc proto-oncogene (p less than 0.01), whereas the negative rate of St-439 was correlated with the gene amplification of c-erb B-2 (p less than 0.01). These data indicate the prognostic value of HPA and St-439 and also the relationships between the gene amplifications and carbohydrate structures in breast cancer cells.
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PMID:The prognostic value of tumor-associated carbohydrate structures correlated with gene amplifications in human breast carcinomas. 168

To elucidate the possible roles of proto-oncogenes and growth factors in estrogen-regulated cell proliferation of human breast and gynecologic cancers, we have determined the gene expressions of c-myc, transforming growth factor-alpha and beta 1 (TGF-alpha, beta 1) and epidermal growth factor receptor (EGFR) in a number of these cancer cell lines by using an intron-Differential (ID) RNA/PCR method, which differentially identifies the amplified cDNA from PCR products of genomic DNA contaminants. With this method, we demonstrated the expression of these genes, except EGFR, in an estrogen-dependent breast cancer cell line (CAMA-1). Our results show that TGF-alpha/EGF does not function as an autocrine factor in this cell line. Accordingly, it is unlikely that the TGF-alpha/EGFR system participates as a mediator in the estrogen-induced cell proliferation of CAMA-1 cells. The ID RNA/PCR method is a rapid, sensitive and specific technique for mRNA phenotyping and will have great clinical utility.
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PMID:Survey of oncogene and growth factor/receptor gene expression in cancer cells by intron-differential RNA/PCR. 169 73

Two new breast tumor cell lines (UISO-BC-1 and UISO-BC-2) have been established from pleural effusions obtained from patients with confirmed diagnosis of breast cancer. Cytogenetic investigation shows several numerical and structural aberrations in both cell lines. Each cell line appears to have distinctive karyotypic aberrations. Although a common marker chromosome was not found in both cell lines, several breakpoints (i.e., 1q11, 3q11, 7p11, 9q11, and 13q11) were commonly involved in the marker chromosomes of both lines. Double minute (dmin) chromosomes were also observed in these two cell lines. Sixteen oncogene probes were used to study the oncogene amplification and overexpression; among these, only neu and c-myc probes detected multiple gene copies. A 10-fold amplification and a 20-fold overexpression of the neu were observed in the UISO-BC-1 line, whereas a threefold and a fivefold amplification of c-myc were found in UISO-BC-1 and UISO-BC-2, respectively. Moderately enhanced expression (sixfold) of c-myc was also observed in the UISO-BS-2 line. No gross rearrangement of these genes or aberrant RNAs was detected in these tumor cell lines.
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PMID:Chromosome aberrations and oncogene alterations in two new breast tumor cell lines. 170 95

The c-myc, c-erbB-2, hst and int-2 oncogenes are frequently amplified and/or overexpressed in human breast carcinomas. We studied the effect of tamoxifen on RNA levels of these oncogenes in 19 breast cancer patients treated for 3 weeks prior to surgery as compared with 22 control patients. RNA levels were measured by in situ hybridization coupled with computer-aided quantification. c-myc and c-erbB-2 expression was high in the control population (mean values: 23.4 and 29.1 grains/cell respectively) and significantly decreased in the tamoxifen-treated population (mean values: 14.6 and 7.4 grains/cell respectively) (P = 0.018, P = 0.003 respectively); hst and int-2 RNA levels were low (2-6 grains/cell) and not significantly altered by the treatment. There was a correlation between gene amplification and expression for c-erbB-2 (P = 0.0005) and hst (P = 0.02) in the control population. Elevated c-erbB-2 RNA level was correlated with the absence of estrogen (P = 0.02) or progesterone (P = 0.05) receptors. In the ER+ population, the tamoxifen-treated group had significantly lower c-myc expression levels than the control group (P = 0.04) which is in agreement with the estrogen induction of c-myc in ER+ T47D cell line and its inhibition by antiestrogens. Surprisingly, c-erbB-2 expression in the tamoxifen-treated group was significantly diminished in the ER- (P = 0.02) and PR- (P = 0.01) populations. This effect was not observed in the ER- BT474 cell line. These results suggest that in vivo tamoxifen decreases c-myc and c-erbB-2 RNA levels in breast cancer cells via two different mechanisms. To our knowledge this is the first evidence of in vivo down regulation of a gene by tamoxifen in ER- breast cancer cells.
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PMID:Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer. 170 53

The biological activity of interferons (IFNs) is presumed to be mediated through the induction of a number of IFN-inducible genes. IFN-mediated gene induction was examined in two human breast cancer cell lines, MCF-7 and BT-20. Both these cell lines were remarkably responsive to IFNs as a number of IFN inducible genes were rapidly induced. We examined the sensitivity of these genes towards 2-aminopurine (2-AP), a known inhibitor of double-stranded (ds) RNA dependent protein kinase. 2-AP has also been reported to inhibit the induction of IFN-beta 1 in response to dsRNA and the genes c-myc and c-fos in fibroblasts. In both MCF-7 and BT-20 cell lines, 2-AP selectively inhibited the IFN-induced gene responses. 2-AP did not affect levels of the oncogene, HER-2/neu. Tamoxifen (TAM), an antiestrogenic drug, which is known to inhibit the activity of protein kinase C at high concentrations, did not affect IFN-mediated gene induction. Our data is consistent with the concept that the 2-AP sensitive kinase is primarily associated with the IFN-induced gene systems and that positive and negative growth regulating stimuli in breast cancer may require the participation of distinct kinases.
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PMID:A distinct kinase modulates the expression of IFN-inducible genes in human breast cancer cells. 171 33

Amplification of the c-myc and HER2/neu genes was found in 20 and 23%, respectively, of primary breast cancer tissues derived from 282 patients (median follow-up, 74 months). c-myc amplification was observed more frequently in larger tumors (P = 0.01) and in lymph node-positive patients (P = 0.01) but was not associated with age, menopausal status, or with differentiation grade or steroid receptor status. c-myc amplification was strongly negatively correlated with HER2/neu amplification (P less than 0.001). In univariate analysis, amplification of c-myc proved to be a significant predictor of reduced relapse-free and overall survival (for both, P less than 0.001). In multivariate analysis for relapse-free survival, c-myc amplification significantly (P = 0.001) added to the prognostic power of tumor size (P less than 0.001), lymph node status (P less than 0.001), and estrogen receptor status (P = 0.003), with the highest relative failure rate (1.8) after lymph node status (2.2). In this pilot study, c-myc amplification was predictive for outcome, especially among patients with node-negative disease or steroid receptor-positive tumors; 51 and 46% differences in actuarial 5-year recurrence rates when compared to patients with tumors with normal c-myc gene copy numbers, respectively. HER2/neu amplification was not associated with relapse-free survival but weakly with shorter overall survival in univariate analysis (P = 0.035). Only in the relatively small subgroup of steroid receptor-negative tumors, HER2/neu amplification may identify those patients with an increased risk of death. In conclusion, amplification of c-myc is an independent powerful prognosticator, particularly in node-negative and steroid receptor-positive breast cancer, whereas HER2/neu amplification may be of limited prognostic value, only in steroid receptor-negative disease.
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PMID:c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. 173 70

Activation of protooncogenes and constitutive secretion of autocrine growth factors are thought to be involved in the uncontrolled growth of cancer cells. We have attempted to elucidate the role of oncogenes and growth factors in the premalignant progression of human breast epithelial cells by using an immortalized, nontumorigenic, near-diploid human mammary epithelial cell line, HMT-3522, derived from a fibrocystic lesion and established in our laboratory. During propagation in tissue culture, the growth factor requirements of the HMT-3522 cells decreased simultaneously with an amplification and overexpression of the c-myc protooncogene. Other protooncogenes related to human breast cancer were unaltered with regard to gene copy number and expression. In passage 118, in which the most important growth factor still was epidermal growth factor (EGF), we were able to isolate an EGF-independent subline (S2). The EGF independence of S2 was accompanied by an overexpression of the mRNAs for epidermal growth factor receptor (EGF-R), transforming growth factor-alpha, and c-erb-B2 as compared to the EGF-dependent subline (S1). Moreover, by application of a blocking anti-EGF-R antibody, growth of S2 cells in EGF-free medium was inhibited significantly, indicating that EGF-R was involved in an autocrine loop probably with transforming growth factor-alpha as ligand. Neither the late passages of S1 cells nor S2 cells were tumorigenic after subcutaneous transplantation to athymic mice. Our results indicate that c-myc amplification and overexpression are correlated with a decreased requirement for growth factors. Even when these alterations are combined with immortalization and EGF independence, they are insufficient for malignant transformation of these human breast epithelial cells.
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PMID:Altered gene expression of c-myc, epidermal growth factor receptor, transforming growth factor-alpha, and c-erb-B2 in an immortalized human breast epithelial cell line, HMT-3522, is associated with decreased growth factor requirements. 173 82

In breast tumor cell lines, c-myc amplification is frequently associated with estrogen unresponsiveness. We, however, succeeded in characterizing an estrogen-responsive cell line VHB1 derived from a duct cell carcinoma, which exhibits c-myc amplification and overexpression. We therefore studied the effects of estrogen and antiestrogen on c-myc expression in this particular cell line. We also investigated these effects on the expression of c-mil and c-myb oncogenes, also expressed but not amplified in VHB1 cells. Short-(1 h) and long-(72 h) term stimulations were performed. Our experiments showed that estradiol (E2 10(-8) M) was still able to stimulate c-myc expression equally either after short or long-term treatment. In the same way, the antiestrogen 4-hydroxytamoxifen equally decreased c-myc expression but the reversal effect of E2 after long-term antiestrogen treatment was more pronounced than after short-term treatment. The effects of E2 and 4-OH Tam on the expression of the not-amplified c-mil and c-myb oncogenes were stronger than those observed on c-myc expression; however, the E2 reversal effect was identical either after short or long-term antiestrogen treatment. Our results may enlighten some aspects of the complex action of some of the early- and late-growth regulated genes in breast cancer.
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PMID:C-myc overexpression, c-mil, c-myb expression in a breast tumor cell line. Effects of estrogen and antiestrogen. 177 59

In order to investigate further the mechanisms associated with growth inhibition of human breast cancer cells by progestins and nonsteroidal antiestrogens, their effect on c-myc gene expression in T-47D-5 and T-47D cells has been investigated. The c-myc mRNA levels were differentially regulated by the synthetic progestin, medroxyprogesterone acetate and the nonsteroidal antiestrogen, monohydroxytamoxifen, in both cell lines. Antiestrogen treatment caused a persistent decrease in c-myc mRNA levels while the progestin caused a more complex response. Initially c-myc mRNA levels increased approx. 2-fold, this was followed by a decrease and then partial recovery. The end result, however, of each of these treatments is decreased cell number.
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PMID:Differential regulation of c-myc by progestins and antiestrogens in T-47D human breast cancer cells. 182 55


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