Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiology suggests a possible relationship between exposure to power frequency magnetic fields (EMF) and breast cancer. One mechanism through which EMF could stimulate breast cancer induction is via altered expression of oncogenes and/or tumor suppressor genes that regulate normal and neoplastic growth. To evaluate the hypothesis that EMF action in the breast is mediated by alterations in gene expression, transcript levels of c-myc and a battery of other cancer-associated genes were quantitated in human breast epithelial cells exposed to pure, linearly polarized 60 Hz EMF with low harmonic distortion. HBL-100 cells and normal (non-transformed) human mammary epithelial cells were exposed to EMF flux densities of 0.1, 1.0 and 10.0 Gauss (G) for periods ranging from 20 min to 24 h; concurrent sham controls were exposed to ambient fields (<0.001 G) only. Gene expression was quantitated using ribonuclease protection assays. EMF exposure had no statistically significant effect on basal levels of c-myc transcripts in either human breast cell model, and had no effect on alterations in c-myc expression induced by 12-O-tetradecanoylphorbol-13-acetate. Transcript levels of c-erbB-2, p53, p21, GADD45, bax, bcl-x, mcl-1, and c-fos were also unaffected by EMF exposure. These results suggest that EMF is unlikely to influence breast cancer induction through a mechanism involving altered expression of these genes.
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PMID:Gene expression in human breast epithelial cells exposed to 60 Hz magnetic fields. 1042 19

Fas and Fas ligand (FasL) mediate T-lymphocyte cytotoxicity and may also induce physiologic apoptosis in breast epithelium associated with menstruation and cessation of lactation. Altered expression may thus be associated with breast carcinoma progression, chemotherapy response, or outcome. We performed a clinicopathologic analysis of immunohistochemical staining for Fas and FasL, as well as bax, bcl-2, glutathione-s-transferase, HER-2 (c-erbB-2), Ki67, P-glycoprotein, p53, and hormone receptors in pretreatment breast biopsies from 34 patients with locally advanced or limited stage IV breast carcinoma who received preoperative (neoadjuvant, primary) chemotherapy followed by lumpectomy or mastectomy. Neoplastic cells expressed Fas in 44% and FasL in 85% of pretreatment biopsies. Fas immunostaining was more frequent in tumors with larger size (p = 0.02) and pretreatment metastases (p = 0.03). Combined Fas and p53 staining correlated with pathologic complete response (4 of 5 CR versus 6 of 29 other, p = 0.02), as did combined p53 and lack of FasL staining (2 of 5 CR versus 0 of 29 other, p = 0.02), but individually Fas, p53, and lack of FasL immunostaining demonstrated only trends to correlation with CR (p = 0.13-0.15). No other biomarkers correlated with chemotherapeutic response. Neither FasL nor Fas expression was associated with the degree of peritumoral lymphocytic infiltration, or with expression of the other biomarkers. Recurrence was more frequent in Fas-expressing tumors (recurrent cases 7 of 10 Fas positive versus nonrecurrent 8 of 24 Fas positive, p = 0.07). In this patient group, Fas expression is associated with aggressive tumor behavior. Biomarker immunostaining correlates weakly with pathologic response to preoperative chemotherapy, in keeping with complex or heterogeneous tumor-drug interactions.
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PMID:Clinicopathologic Analysis of Fas, Fas Ligand, and Other Biomarkers in Locally Advanced Breast Carcinoma. 1134 71

In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR), c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (> or = 30%) negatively influenced the disease-free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl-2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.
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PMID:Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer. 1141 68

Pancreatic cancer has a very poor prognosis and is a common cause of cancer death in the Western world. Certain genetic alterations may be important in the prognosis of pancreatic cancer. Activation mutations in the K- ras oncogene occur in around 90% of pancreatic cancers, and the overexpression of growth factors epidermal growth factor (EGF), transforming growth factor (TGF)alpha, TGFbetas 1-3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c-erbB-2 and -3 and TGFRbetas 1-3 is common. High mutation levels of cell cycle control genes such as p53, p16, p21, SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such as bcl-2, bcl-XL, and bax. The expression of several of these growth factors and their receptors has been found to be associated with poorly differentiated tumors of an advanced stage and decreased survival. However, the inactivation and loss of expression of p16, p53, and p21, and the expression of several apoptotic genes, such as bax and bcl-2, have not been found to be of any prognostic significance. The expression of wild type p53, however, may predict responsiveness to chemotherapy. TGFbeta1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have found bcl-XL expression to be significantly associated with poor survival. These and newer molecular markers may prove to be important in the choice of future therapies for pancreatic cancer.
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PMID:Molecular prognostic markers in pancreatic cancer. 1202 93

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.
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PMID:Biomarkers for breast cancer. 1214 73

We examined the prognostic value of c-erbB-2, p53, bcl-2 and bax overexpression in breast cancer. Immunostaining for c-erbB-2, p53, bcl-2 and bax gene expression was performed on 121 paraffin-embedded specimens of Stage I, II and III breast cancer patients diagnosed and treated in Hippokration Hospital, Athens Medical School, between 1986 and 1992. The primary tumor from 27 (24.1%), 69 (59%), 18 (15%) and 63 (53.4%) patients stained positively for c-erbB-2, p53, bcl-2 and bax gene expression, respectively. Significant correlations were found between bax overexpression and age (P=0.04), tumor size (P=0.02) and disease stage (P=0.001), while no other significant associations were found between other molecular markers and clinical or histological parameters. None of the individual molecular markers examined proved to be independent prognostic factor for patients with breast carcinoma. C-erbB-2, p53, bcl-2 and bax genes have limited prognostic value. An approach that combines several molecular markers with established clinicopathological criteria may help physicians make more accurate predictions of prognosis in patients with breast cancer.
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PMID:Molecular markers in breast cancer: can we use c-erbB-2, p53, bcl-2 and bax gene expression as prognostic factors? 1496 83

Survivin is a recently discovered member of the family of proteins that inhibits apoptosis. This anti-apoptotic compound can be detected in most types of cancer and expression is associated with a poor prognosis. We, immunohistochemically, investigated the expression of survivin in breast carcinomas and intraductal epithelial neoplasia of the breast to determine whether expression of this protein is associated with clinicopathological parameters such as grade, stage, mitotic rate. In 34 out of 43 cases (79.1%) of breast carcinoma and 22 out of 62 cases (35.4%) of intraductal epithelial neoplasia with mild, moderate and severe ductal epithelial, cell hyperplasia stained positively for survivin. None of the histological parameters analyzed were significantly correlated with survivin expression in breast carcinomas. In the carcinoma cases, survivin expression was positively correlated with expression of bcl-2, but was not correlated with expression of p53, bax, c-erbB-2 and estrogen, or progesterone. Some of the intraductal epithelial neoplasia cases with moderate or severe ductal epithelial hyperplasia stained positively for both survivin and p53. Breast carcinomas exhibited a significant expression of survivin, p53, and bcl-2 compared to breast with intraductal epithelial neoplasia. Survivin was not correlated with any of the clinicopathological parameters studied, however it could be a useful tool in early carcinomas and florid, severe ductal epithelial hyperplasia.
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PMID:Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal intraepithelial neoplasia (DIN 1a). 1514 58

Clear cell carcinoma of the ovary is considered to be a specific subtype among the epithelial ovarian malignancies. To characterize clear cell carcinomas in early FIGO stages (I-II) with regard to clinical and biological properties, a retrospective study was performed to compare these tumors with other histological subtypes. From a complete series of 226 patients with epithelial ovarian carcinomas in FIGO stages I-II, 28 patients with clear cell carcinomas were selected and the clinical and biological characteristics of these tumors were compared with the remaining non-clear cell carcinomas. All patients underwent primary staging laparotomy followed by adjuvant radiotherapy or chemotherapy. The apoptosis regulators p53, bcl-2 and bax, and the growth factor receptors EGFR and HER-2/neu were analyzed by immunohistochemical techniques and DNA analysis was performed by flow cytometry. Clear cell carcinomas stained negative for p53 significantly more often than other histological subtypes. Positive EGFR staining was seen more frequently in serous carcinomas than in the clear cell carcinomas. Aneuploid DNA status was seen more frequently in clear cell carcinomas than in other histological subtypes and tetraploid tumors made up 50% of the non-diploid tumors. Clear cell tumors were frequently (64%) found in FIGO stages IC and IIC and this was more common than for non-clear cell tumors. No difference was found in the rate of tumor recurrences or survival for patients with clear cell and non-clear cell carcinomas. Clear cell carcinomas of the ovary should be regarded as a separate entity among the epithelial ovarian carcinomas and they differ with regard to both clinical and biological characteristics when compared with non-clear cell tumors.
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PMID:Clinical and biological characteristics of clear cell carcinomas of the ovary in FIGO stages I-II. 1558 38