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

We studied the effect of recombinant tumor necrosis factor (TNF) on selected leukemic and breast cancer cell lines. Based on their sensitivity to TNF in the presence or absence of cycloheximide (CHX), these cell lines could be categorized into three phenotypes: SS, cells that are spontaneously sensitive to TNF; RS, cells that are normally resistant to TNF but are killed in the presence of CHX; and RR, cells that are resistant to TNF irrespective of the presence of CHX. The effect of TNF on expression of c-myc, N-ras, and Ha-ras oncogenes was also studied in these cell lines. Transient, minimal suppression of c-myc was observed in one cell line (Raji), and an inconsistent stimulation of c-myc in another (MCF-7.OCI). No correlation was observed between the effect on oncogene expression and TNF sensitivity.
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PMID:Oncogene expression and cytotoxic activity of tumor necrosis factor against human cancer cells. 266 84

A serious effort has been made to identify and characterize mutations that frequently occur during the evolution of primary human breast cancer. Some of these mutations involve amplification of protooncogenes (c-myc, c-erbB-2, and int-2) that have been shown to contribute to experimentally induced breast cancer in mouse model systems. Tumor development in mice containing the c-myc or c-erbB-2 transgene suggests that the cellular and developmental contexts in which the genes are expressed define their relative contribution to tumorigenesis. Homozygous deletions or loss of heterozygosity (LOH) represent another type of mutation that has been frequently observed on four chromosomes (1q, 3p, 11p, and 13q) in tumor DNA. They are thought to unmask recessive mutations (LOH) that inactivate or remove (homozygous deletion) suppressor genes that regulate normal cell proliferation. Attempts to determine whether specific mutations are associated with certain clinical parameters have led to the controversial hypothesis that some mutations may be useful prognostic indicators of the post-surgical course of the disease. The current results underscore the necessity for much larger, better control studies to unambiguously define the potential of such mutations as clinical markers.
Breast Cancer Res Treat 1989 Jul
PMID:Genetic alterations in primary breast cancer. 266 53

Amplification and overexpression of the c-myc protooncogene have been observed in 22 to 32% of primary human breast cancers, yet the exact role of this gene in mammary tumor progression is unclear. We sought to elucidate this role by overexpressing cloned myc genes in the human breast carcinoma cell line MCF-7. We found that augmented myc RNA levels were associated with slower in vitro growth rates, but that estrogen receptor levels, the requirement for estrogen for in vivo growth in castrated athymic nude mice, and sensitivity to the antiestrogen, tamoxifen were not altered. Furthermore, chemosensitivity to the cytotoxic agent, Adriamycin, was not affected. Lastly, overexpression of a transfected myc gene did not suppress endogenous myc levels unlike the findings in lymphoma cells. Thus our data suggest that the effect of augmented myc expression in human breast cancer cells is complex and may not induce more malignant patterns of growth as has been suggested for other human cancers.
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PMID:Effects of c-myc overexpression on the growth characteristics of MCF-7 human breast cancer cells. 266 48

We review and discuss data on the genetic alterations documented in human breast carcinomas at the molecular level. These alterations may result in: 1) deletion of genetic material (chromosome 11p, 13q, 3p, 1q, 17p); 2) amplification of genes or entire chromosomal segments (c-myc, c-erb-B2, locus DF3/PUM, loci on 11q13); 3) rearrangements (c-myc); 4) point mutations (c-ras). Presently available informations do not allow the development of cohesive pathogenetic models but indicate that the molecular basis of human breast cancer is heterogeneous.
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PMID:Genomic alterations in human breast cancer: a review. 268 75

Enhanced c-myc oncogene expression associated with peptide mitogen-stimulated cell growth is primarily a result of a post-transcriptional event involving increased mRNA stability. We have recently shown that estradiol stimulates c-myc expression in estrogen receptor-positive human breast cancer cells. In this report, we show that in estrogen-responsive MCF-7 cells, estradiol stimulated the c-myc gene exclusively at the transcriptional level, increasing c-myc mRNA transcription more than 10-fold within 20 min, while having no effect on the c-myc mRNA half-life of 18 min. In addition, pretreatment of the cells with cycloheximide did not prevent induction of the c-myc oncogene, indicating a primary effect of estrogen. Furthermore, the elevated level of c-myc mRNA in estrogen-independent MDA-MB-231 cells was due primarily to a more stable c-myc mRNA with a half-life of 49 min, in the absence of enhanced transcription. These results indicate that different mechanisms of regulation of c-myc oncogene expression exist in hormone-dependent and -independent human breast cancer cells.
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PMID:Transcriptional regulation of c-myc oncogene expression by estrogen in hormone-responsive human breast cancer cells. 304 26

The MDA-468 human breast cancer cell line has an amplified epidermal growth factor (EGF) receptor gene (20 x) and correspondingly overexpresses the EGF receptor. Since this cell line is growth inhibited by supra-physiological levels of EGF in tissue culture, it has been possible to select variant cells which have lost the chromosome bearing the amplified EGF receptor domain and which are capable of growing in high levels of EGF. One such cell line (MDA-468-S4) shows an absolute requirement for EGF for growth in anchorage-independent tissue culture conditions. We have utilized MDA-468 and MDA-468-S4 to examine the intracellular transduction of EGF signals leading to growth inhibition and proliferation, respectively. We report that in anchorage-independent conditions, pertussis toxin can abrogate both the EGF-dependent growth inhibition in MDA-468 cells and the EGF-dependent cell proliferation in MDA-468-S4 cells. This inhibition is paralleled by the ADP-ribosylation of an endogenous 41,000-dalton membrane protein in both MDA-468 and MDA-468-S4 cells. In contrast, the toxin does not prevent the transient, augmented expression of c-myc and c-fos mRNA seen in response to EGF in both cell types. These data suggest 1) the notion of more than one simultaneous, parallel, intracellular EGF-dependent signal transduction pathway and 2) G-protein involvement in at least one pathway mandatory for the growth modulating responses to EGF in anchorage-independent conditions, but distinct from that inducing c-myc and c-fos mRNA expression.
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PMID:G-protein-mediated epidermal growth factor signal transduction in a human breast cancer cell line. Evidence for two intracellular pathways distinguishable by pertussis toxin. 312 85

Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.
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PMID:A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas. 316 70

To investigate if the estrogen control of the tumorigenic phenotype of breast cancer cells was mediated through activation of the c-fos protooncogene, we examined the expression of this oncogene in MCF-7 cells. In cells synchronized by double thymidine blockade, the peptide growth factors transforming growth factor alpha and epidermal growth factor increased c-fos mRNA levels 6-fold above controls after 30 min of treatment. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, increased c-fos mRNA levels 4- to 5-fold above control. 17 beta-Estradiol, a growth stimulator, increased c-fos mRNA levels less than 2-fold above control levels, while progesterone, vitamin D3, dihydrotestosterone, and dexamethasone had little effect on c-fos mRNA levels. In contrast, 17 beta-estradiol treatment initially diminished the c-myc RNA level after 30 min of treatment and resulted in an elevation of c-myc by 2.5 h after initiation of treatment. We conclude that c-fos induction in these cells is growth related and accompanies stimulation by transforming growth factor alpha and epidermal growth factor. 17 beta-Estradiol, on the other hand, induced much smaller increases in c-fos mRNA levels, suggesting an alternative or more complex mechanism of cellular stimulation.
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PMID:Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells. 325 9

The restriction analysis of breast cancer DNA revealed amplification of c-myc and c-Ha-ras oncogenes in 3 of 19 and 4 of 22 carcinomas, respectively. In two tumours containing amplified c-Ha-ras1-fragment an additional ras-band absent in unchanged lymphatic nodule and blood leukocytes of the same patients was revealed. Amplification of myc gene was registered in poorly differentiated carcinomas with high metastatic potential. c-Ha-ras1 activation (amplification and elevated expression) was identified in nonaggressive tumours with prolonged progression.
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PMID:[Amplification, rearrangement and expression of the c-myc and c-Ha-ras1 proto-oncogenes in patients with breast cancer]. 328 21

The effects of estradiol (E2) on c-myc proto-oncogene expression were studied in the estrogen receptor (ER)-positive human breast cancer cell line, MCF-7. A biphasic modulation in c-myc mRNA levels occurs during the first 24 h of E2 (1 nM) exposure and in the absence of changes in MCF-7 culture growth, with transcript levels rising 4-6-fold within 1 h, returning to near base-line level after 3-6 h, and increasing again after 24 h of exposure. In contrast, the growth-inhibiting antiestrogen, tamoxifen (1 microM), reduces c-myc to 20% of the pretreatment level within 3-6 h of exposure, and this early decline is followed by a gradual return toward base-line level after continuous 72-h treatment. In ER-negative cells there is no change in c-myc expression following E2 exposure. MCF-7 nuclear runon assays show that c-myc transcription rates remain unchanged from base line for 24 h after E2 administration; as well, cycloheximide inhibition of protein synthesis superinduces c-myc expression and prevents E2 modulation of transcript levels. These results indicate that post-transcriptional modulation of c-myc by E2 is mediated by a labile degradative protein or otherwise dependent on active protein synthesis. We also developed MCF/nm and MCF/dm sublines by transfecting normal cells with human c-myc exons 2-3, transcriptionally driven by a retroviral long terminal repeat. Expression of the transfected c-myc genes in these sublines remains constant and elevated 10-fold, while transcript levels from the endogenous proto-oncogene continue to be modulated by E2. These findings suggest that in ER-positive breast cancer cells, E2 can modulate c-myc mRNA levels by a post-transcriptional mechanism that depends on gene sequences upstream from c-myc exon 2.
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PMID:Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells. 329 Feb 9


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