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

The nuclear transcription factor Fos is inducible by both steroid hormones and peptide growth factors. It thus forms a potential point of interaction between steroid hormone- and growth factor-directed pathways and may be critical in the subversion of steroid hormone control in breast cancer. In this light, the present study has used immunocytochemistry to demonstrate in clinical primary breast cancer that Fos expression is indeed significantly associated with a failure to respond to endocrine therapy, with preliminary analysis revealing a survival advantage for those patients whose tumours lacked Fos. Sustained elevated levels of Fos expression were significantly associated with further factors, notably peptide growth factors and their receptors (e.g., EGFR, TGF alpha), as well as with the proliferation marker Ki-67, which have been linked previously to endocrine insensitivity in breast cancer. In contrast, there appeared to be a trend for Fos to be absent in those tumours expressing markers of endocrine responsiveness (e.g., oestrogen receptor [ER], and also ER-mediated markers i.e., PR, pS2 or bcl-2). Interestingly, many of these trends were maintained in ER+ patients, suggesting that Fos may be of importance in directing loss of endocrine sensitivity in ER+ disease.
 ...
PMID:Immunocytochemical localization of Fos protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. 765 91

Transcripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGF1, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth-factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post-radiation fibrosis lesions by slot-blot autoradiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. The drugs modulated the levels of the anti-oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub-types defined by the presence of alpha-sm-actin (myofibroblasts) or EDB-fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi-gene but also a multi-tissue phenotype.
 ...
PMID:Quantitative variation of proto-oncogene and cytokine gene expression in isolated breast fibroblasts. 776 44

Epidermal growth factor (EGF) is a mitogenic peptide that binds to surface membrane receptors (EGFR) of breast cancer cells. After binding, secondary transmitter molecules are activated by tyrosine phosphorylation of the intracellular receptor domaine. The activity of the EGF/EGFR system can be modulated by a variety of chemically unrelated compounds including cytostatic agents. The purpose of our present study was to determine the effects of mitotic inhibitors on EGF receptor binding on human breast cancer cells. We found that MDA-231 and MDA-468 cells bind substantially more [125I]EGF after preincubation with docetaxel, vinblastine and vincristine. This effect was concentration- and time-dependent, reaching a maximum at 3000 ng/ml and 48 h incubation for docetaxel, and 100 ng/ml and 48 h incubation for vinca alcaloids. Subsequent experiments showed an increase in the rate of EGF binding as well as maximal binding capacity. Scatchard analysis of binding experiments under equilibrium conditions indicated that this was due to an increase in the number of apparent EGF binding sites. Modulation of EGF receptor binding by docetaxel, vinblastine, and vincristine was not detectable when isolated membranes were used, indicating that intact cytoplasmatic mechanisms are required for the upregulation of EGF receptors.
 ...
PMID:Effects of the microtubule-disturbing agents docetaxel (Taxotere), vinblastine and vincristine on epidermal growth factor-receptor binding of human breast cancer cell lines in vitro. 783 45

Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER-/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNAse I hypersensitive site patterns for the EGFR gene in ER+ vs. ER- cells implicates regions of the EGFR first intron in up-regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER-/EGFR+ stage.
Breast Cancer Res Treat 1994
PMID:Mechanisms of EGF receptor regulation in breast cancer cells. 788 Nov 1

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
Breast Cancer Res Treat 1993 Dec
PMID:Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. 791 62

The type 1 family of growth factor receptors includes the EGFR, c-erbB2, c-erbB3, and c-erbB4. All four members of the family are expressed in breast cancer. The EGFR gene and more frequently the c-erbB2 gene are amplified in a proportion of cases. In addition to increased expression as a result of gene amplification, overexpression of perhaps all of the receptors also appears to occur, probably as a result of increased mRNA transcription. Overexpression may have prognostic value and may predict response to current therapies. Finally these GFR proteins represent targets for new types of chemotherapeutic agents.
Breast Cancer Res Treat 1994 Jan
PMID:The type I growth factor receptors in human breast cancer. 791 66

Recent progress in molecular biology has revealed that the proliferation of breast cancer is controlled by various growth factors and their receptors. In particular, the amplifications and products of oncogenes which code growth factors and receptors can be different indicators of clinical malignancy from the conventional prognostic factors. We investigated the relation of c-erbB-2 and int-2 gene amplification, expression, ER and EGFR with clinical characteristics. In retrospective study, the cumulative 10-year survival rate of patients with c-erbB-2 and int-2 gene amplification was significantly lower than in patients without amplification. In 72 cases with tumor diameter less than 3.0 cm, which can be an indication of breast preservation surgery, the survival rates of patients in these gene amplified groups were significantly lower than in the non-amplified groups. As for prospective study, the results were the same as those from retrospective study. These data show that the cases with these gene amplification have a high biological malignancy and high risk of recurrence to distant organs, despite the small tumor diameter.
 ...
PMID:[Abnormalities and clinical characteristics of growth factors and receptor systems in breast cancer]. 791 99

For the integration of new cell biological prognostic factors in daily clinical practice, we need to know not only their prognostic power with respect to prediction of relapse free and overall survival, but also their possible relation to response to endocrine therapy or chemotherapy in order to select adequate treatment for each patient. A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficult to predict the response to treatment accurately. A valuable prognostic factor can be a worthless predictive factor for endocrine therapy or chemotherapy, and vice versa. High tumour levels of ER, PGR, AR and PS2 protein predict a relatively good response to endocrine therapy, whereas EGFR positivity, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high u-PA levels indicate a good chance of a poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, whereas MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low risk patients and type of systemic treatment and can be used as targets for new treatment modalities.
 ...
PMID:Prognostic factors and response to therapy in breast cancer. 801 96

In a retrospective study of 319 primary breast cancers, we show that an immunoenzymatic assay of a solubilized fraction of EGF receptors indicates a prognostic value for EGFR which is in contradiction with some (but not all) other studies. It appears that different methodological approaches of measuring EGFR are not equivalent in terms of prognostic power. We emphasize the need for rigorous multicentric standardization and quality control of assays, followed by multistep validation of parameters oriented towards clinical use.
Breast Cancer Res Treat 1994 Jan
PMID:Prognostic value of a solubilized fraction of EGF receptors in primary breast cancer using an immunoenzymatic assay--a retrospective study. 801 65

Activation of cellular or c-oncogenes and loss of function of suppressor genes appears to be the key event in the formation of most human cancers. Altered forms of these genes or their protein products have the potential to provide a new generation of cancer markers. As cancer markers, the most useful application of c-oncogenes and suppressor genes so far, has been in providing prognostic information. The correlation of N-myc gene amplification with poor prognosis in neuroblastoma was one of the first examples of prognostic data supplied by a c-oncogene. Most, but not all investigators, find that either amplification or increased expression of c-erbB-2 gene correlates with poor prognosis in breast cancer. Other potential prognostic markers in breast cancer include amplification of the c-myc gene, and increased expression of both EGFR and p53 protein. Although c-oncogenes and suppressor genes have the potential to supply prognostic information in a broad range of cancers, many of the results are still preliminary with conflicting conclusions.
 ...
PMID:Cellular oncogenes and suppressor genes as prognostic markers in cancer. 812 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>