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

We have performed an analysis of ras, c-myc, c-myb, c-erbB1 and c-erbB2 oncogenes in 100 surgical samples of human breast carcinomas. No point mutations have been detected at the 12th codon of c-Ha-ras and c-Ki-ras in 40 and 65 breast cancer DNAs, respectively. One out of 65 samples showed a 50-fold amplification of c-Ha-ras that, however, was not overexpressed. Alterations in the structure of c-myc, c-myb c-erbB1 and c-erbB2 oncogenes were sporadically observed. In 20 tumour samples, the study of expression of a series of oncogenes revealed that c-Ha-ras was the predominantly transcribed gene among the ras gene family whereas c-fos appeared the most constantly and significantly expressed nuclear oncogene.
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PMID:Structure and expression of oncogenes in surgical specimens of human breast carcinomas. 329 44

In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do not transform normal cells in culture. In experimental models cooperation between two oncogenes can induce transformation of early passage cells, and this has become the basis of an hypothesis for multistep carcinogenesis. Proto-oncogene products also show sequence homology to various components in the mitogenic pathway (growth factors, growth factor receptors, signal transducing proteins and nuclear proteins), and it has been postulated that they may cause deregulation of the various components of this pathway. In human tumours single or multiple oncogene activation occurs. The pattern of oncogene activation in common solid malignancies is not consistent within any one class of tumour, nor is it uniform between classes, with three exceptions. In neuroblastoma, breast cancer, and perhaps in lung cancer there is relatively consistent activation of N-myc, neu, and c-myc/N-myc, respectively. Amplification of these genes generally correlates with poor prognosis. The introduction of methods for the direct study of oncogene transcription and their products will undoubtedly broaden our vision of cancer biology in man and, hopefully, add diagnostic and prognostic precision to tumour typing.
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PMID:Cellular oncogenes in neoplasia. 331 99

We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c-myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c-myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer.
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PMID:Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. 333 Jul 85

DNAs from fifty-three primary breast cancers were hybridized with 16 different proto-oncogene or oncogene probes. Abnormalities of one or more of five proto-oncogenes were found in fifty-eight percent of tumors at the time of mastectomy. Amplification of c-myc and c-erbB-2, and allelic deletions of c-ras-Ha and c-myb were the most common abnormalities. The presence of altered proto-oncogenes correlated with clinical stage of the cancers. Fifteen of 43 evaluable tumors of stages I to III recurred, and four of five evaluable stage IV tumors progressed within 16 to 24 months of surgery. All but one of the cancers that recurred or progressed had detectably altered proto-oncogenes (P less than .001). Analysis of proto-oncogenes may have prognostic value in breast cancer.
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PMID:Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease. 347 61

Regulation of c-myc expression is known to be sensitive to a variety of mitogenic stimuli in various cell types. Since estrogen is a well documented mitogen of estrogen-responsive human breast cancer (HBC) cells, we studied the influence of estradiol and its antagonist tamoxifen on the expression of c-myc in HBC cell lines. Using Northern hybridization analysis, we monitored the accumulation of c-myc mRNA in a number of HBC cell lines. The cell lines studied included the estrogen-responsive, estrogen receptor positive (ER+) MCF-7, T-47D, the nonresponsive, estrogen receptor negative (ER-) MDA-MB-231, BT-20, and a nontumorous breast cell line, HBL-100. The effects of endogenous estrogen were minimized by culturing the cells in medium containing 10% (v/v) charcoal-treated fetal bovine serum and tamoxifen (10(-6) M) for 48 h prior to estradiol (10(-7) M) treatment. In the ER+ cell lines the addition of estradiol resulted in a noticeable increase in c-myc expression after 15 min with a maximal (greater than 10-fold) induction in 1-2 h. In the ER- cell lines the level of c-myc mRNA was high and was unaffected by estrogen or tamoxifen; in the ER- cancer cell lines, neither amplification nor rearrangement of the c-myc gene was observed. In contrast, the expression of another oncogene, c-H-ras, remained constant in both ER+ and ER- cell lines and was insensitive to estrogen and antiestrogen. These results suggest that regulation of c-myc expression may be an important step in estrogen-induced proliferation of HBC cells.
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PMID:Stimulation of c-myc oncogene expression associated with estrogen-induced proliferation of human breast cancer cells. 367 90

Radioimmunotherapy (RIT) in breast cancer patients using I-131-chimeric L6 (ChL6) and in human breast cancer xenografts in nude mice using Y-90-1,4,7,10-tetraazacylododecant N,N',N",N"'-tetraacetic acid-peptide ChL6 (Y-90-ChL6) has shown promise. Tumor cell response to low-dose rate (5-25 rads/h) irradiation from Y-90-ChL6 RIT, therefore, was correlated with levels of tumor cell mRNA for selected genes linked to programmed cell death (apoptosis). Three groups of 10-16 mice with 1-2 HBT 3477 xenograft tumors were treated with 100, 150, or 250 microCi Y-90-ChL6. Three tumors were taken before and two tumors each were taken 3, 6, and 24 h after injection of 150 microCi Y-90-ChL6. Tumor expression of mRNA was amplified by PCR for p53, PIC1, c-myc, and transforming growth factor-beta 1; quantitated; and standardized to N-ras. Tumors received radiation doses of 2000, 3000, and 5000 rads, respectively, for the groups of mice that received 100, 150, and 250 microCi Y-90-ChL6, and tumor regression occurred in each group, with mean tumor volumes decreased by 10, 50, and 95% at nadir after Y-90-ChL6 injection. At the highest dose level, 30% of mice had complete remissions, and no treatment deaths occurred, although tumors subsequently recurred. Continuous up-regulation of transforming growth factor-beta 1 and c-myc mRNA expression was observed from 3 to 24 h after treatment. Expression of p53 and PIC1 increased at 3 h and subsequently decreased to the untreated control levels. These observations are consistent with previous observations of early responses of p53 and PIC1 to cellular DNA damage and subsequent G1 cell cycle arrest or apoptosis. Apoptosis-associated gene expression patterns observed in this tumor model provide evidence that changes are initiated in the first 24 h of RIT associated with radiation doses of 100-700 rads. These preliminary data suggest that insight into the molecular basis of RIT-induced tumor regression may be gained by further studies using different radiation doses.
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PMID:Yttrium-90 chimeric L6 therapy of human breast cancer in nude mice and apoptosis-related messenger RNA expression. 749 56

We established several immortalized human T cell lines by cotransfecting primary lymphocytes derived from breast cancer patients with human c-myc and human c-Ha-ras oncogenes. A CD8 positive (CD8+) killer T cell line, FT-8, exhibited in vitro specific cytotoxicity to a human breast cancer cell line, MCF-7. The FT-8 cells suppressed the growth of MCF-7 cells transplanted to athymic mice. The cytotoxic reaction was caused via T cell antigen receptor (TCR) on MCF-7 cells, because monoclonal antibodies against the TCR inhibited the cytotoxicity of FT-8 cells. The TCR (alpha) cDNA of FT-8 was cloned by using a PCR amplification technique and expressed by a cell-free in vitro translation system. The TCR (alpha) protein recognized a target antigen of 32 KDa on MCF-7 cells.
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PMID:The detection of a breast cancer antigen on MCF-7 cells reactive with the TCR (alpha) of a specific killer T cell line. 750 45

Polyamines are excellent stabilizers of triplex DNA. Recent studies in our laboratory revealed a remarkable structural specificity of polyamines in the induction and stabilization of triplex DNA. 1,3-Diaminopropane (DAP) showed optimum efficacy amongst a series of synthetic diamines in stabilizing triplex DNA. To utilize the potential of this finding in developing an anti-gene strategy for breast cancer, we treated MCF-7 cells with a 37mer oligonucleotide to form triplex DNA in the up-stream regulatory region of the c-myc oncogene in the presence of DAP. As individual agents, the oligonucleotide and DAP did not downregulate c-myc mRNA in the presence of estradiol. Complexation of the oligonucleotide with 2 mM DAP reduced c-myc mRNA signal by 65% at 10 microM oligonucleotide concentration. In contrast, a control oligonucleotide had no significant effect on c-myc mRNA. The expression of c-fos oncogene was not significantly altered by the triplex forming oligonucleotide (TFO). DAP was internalized within 1 h of treatment; however, it had no significant effect on the level of natural polyamines. These data indicate that selective utilization of synthetic polyamines and TFOs might be an important strategy to develop anti-gene-based therapeutic modalities for breast cancer.
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PMID:Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming oligonucleotide in MCF-7 breast cancer cells. 756 74

To find early and sensitive indicators of treatment response in breast cancer, we studied the mRNA levels of proliferation-related genes during growth arrest of the human breast cancer cell lines T47D and MCF7. A sensitive reverse transcriptase-PCR (RT-PCR) technique was used in order to monitor gene expression in small samples of cells. Estrogen-depletion and treatment with tamoxifen effectively induced a G1-arrest in both cell lines, accompanied by a decrease of the mRNA levels of histone H4, cyclin A, cyclin D1, and c-myc. Cyclin A expression decreased most strongly: up to 32-fold within 7 days. The expression of c-fos and WAF1 increased during growth arrest. In conclusion, significant changes of the levels of proliferation-related mRNAs, induced by growth arrest, can be measured in small samples of breast carcinoma cells using RT-PCR. Especially the decrease of the cyclin A mRNA level seems a potential early indicator of clinical response to tamoxifen therapy in breast cancer patients.
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PMID:Growth arrest associated changes of mRNA levels in breast cancer cells measured by semi-quantitative RT-PCR: potential early indicators of treatment response. 758 69

The retinoblastoma (RB) tumour suppressor gene has been associated not only with retinoblastoma but also with several other tumours like osteosarcoma, small cell lung carcinoma and prostate and breast cancer. We have studied the incidence of RB gene alterations in 96 primary breast tumours using Southern blotting techniques. The outcome has been related with patient and tumour characteristics, oncogene amplifications, p53 mutations and prognosis. RB gene alterations were found to occur more frequently in estrogen receptor (ER)-positive than in ER-negative tumours and less frequently in tumours with oncogene amplification than in tumours without oncogene amplification of HER2/neu, c-myc or 11q13. RB gene alteration was observed in tumours both with and without a p53 gene mutation. Data on 87 patients (mean age, 59.6 years; median follow-up, 108 months) and RB gene alterations revealed a significant association between the frequency of RB gene alterations and node-negative patients (p < 0.01) or smaller (< 2 cm) tumours (p < 0.01), but no relation with age, differentiation grade or (relapse-free) survival. Patients with and without RB gene alterations showed the same relapse-free and overall survival.
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PMID:Association between RB-1 gene alterations and factors of favourable prognosis in human breast cancer, without effect on survival. 761 56


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