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)

Human endometrial adenocarcinoma cells (Ishikawa line) constitutively express c-erbB2 coded oncoprotein p185erbB2 (p185) which is believed to be an orphan receptor for an unknown growth factor. Since we have shown that expression of p185 in primary lesions of endometrial cancer correlates well with high frequency of lymph node++ metastases and that the metastatic cells in the nodes strongly expressed p185, the role of the oncoprotein in processes of metastases was studied. Culturing the cells in the presence of 15% FCS and with monoclonal antibody to the extracellular domain of p185 (CB-1) inhibited cell growth and attenuated p185 expression on Western blotting, whereas no change occurred with the control antibody. Cells cultured without FCS achieved only approximately 1/3 growth compared to cells with FCS, and further suppression of growth was observed after adding CB-1. When cells were cultured on human term amnion, basement membrane invasion with p185 expression was observed. In nude mice, intraperitoneal seeding resulted in implant formation which was also associated with positive p185 as well as cyclin immunohistochemistry. In the two experiments, treatment of cells with CB-1 inhibited invasion or implant formation. The present study suggests that a signal through p185 receptor molecules acts as a trigger for early proliferation, and interaction with the host may enhance up-regulation of p185.
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PMID:[Role of p185c-erbB2 in endometrial cancer growth in vitro]. 135 38

In an attempt to understand the antiproliferative effects of progestins in endometrial cancer, we have examined the effects of the potent progestin, medroxyprogesterone acetate (MPA), on the cell proliferation and the expression of transforming growth factor (TGF) alpha and beta genes in human endometrial adenocarcinoma cell lines. The two cell lines used were Ishikawa, var 1, and HEC-50. In addition, the effects of exogenous TGF-alpha and anti-epidermal growth factor (EGF) receptor monoclonal antibody on cell proliferation were determined. Incubation of both cell lines with MPA resulted in a time- and dose-dependent inhibition of cell proliferation. Half-maximal growth inhibition was observed at 0.6 nM. In Ishikawa cells, the relative abundance of TGF-alpha was significantly reduced by MPA. A significant decrease in TGF-alpha mRNA was apparent 6 h after exposure to MPA and a further decrease was seen 12-24 h after addition of the progestin. The concentration of TGF-alpha immunoreactivity in conditioned medium of MPA-treated cells was also significantly reduced compared to control cultures. MPA had no effect on TGF-alpha expression by HEC-50 cells. EGF mRNA was not detected by Northern blot analysis in either cell type. MPA had no significant effect on EGF receptor mRNA abundance but resulted in a small increase in EGF receptor number in Ishikawa cells. Anti-EGF receptor monoclonal antibody (0.6-6 nM) inhibited Ishikawa cell growth but had no effect on HEC-50 cell proliferation. Exogenous TGF-alpha stimulated proliferation of both cell lines, but Ishikawa cells were significantly more sensitive to exogenous TGF-alpha than HEC-50 cells. Furthermore, TGF-alpha could reverse the growth inhibitory effects of MPA on Ishikawa cells. A decrease in TGF-beta mRNA abundance was also observed in MPA-treated Ishikawa and HEC-50 cells. This effect was of small magnitude, variable, and only observed after prolonged exposure to MPA. These observations are consistent with the hypothesis that the antiproliferative effects of progestins on Ishikawa cells are mediated by decreased expression and autocrine action of TGF-alpha. Since similar growth inhibition is also seen in the HEC-50 cells in which progestins have no effect on TGF-alpha expression, additional mechanisms are likely to be involved in the antiproliferative effects of progestins in human endometrial cancer.
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PMID:Transforming growth factor gene expression in human endometrial adenocarcinoma cells: regulation by progestins. 183 51

The expression of both the nuclear protein p53 tumor suppressor gene product and the transmembrane C-erbB-2 protein oncogene product (p185) correlates to risk factors and outcomes in different tumor types. Their value as prognosticators in endometrial adenocarcinoma of endometrioid type (EC) has not been determined. Paraffin sections were examined immunohistochemically to study the expression of p53 protein and p185 in 112 patients with EC. p53 protein was overaccumulated in 34% and p185 in 13% of the tumors. p53 protein correlated with mitotic count and nuclear grade. Both p53 protein and p185 correlated significantly with outcome. However, they did not correlate with each other or with architectural grade or stage (which defines a high risk group), indicating a role as adjuvant prognosticators in EC. Stage and outcome did correlate, however. Both p53 protein and p185 antibodies work well on routine, formalin-fixed, paraffin-embedded tissue and are easily used in routine diagnostic procedures.
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PMID:p53 protein and c-erbB-2 protein (p185) expression in endometrial adenocarcinoma of endometrioid type. An immunohistochemical examination on paraffin sections. 791 77

This review examines methods of assessing the prognosis of uterine tumors published in the past year. Evaluation of mitosis counts has shown that mitotically active leiomyomas without cytologic atypia follow a benign course; furthermore, the mitotic index does not differentiate endometrial hyperplasia from adenocarcinoma. 'Vascular invasion-associated changes' (VIAC) have been identified as a new prognostic factor for stage 1 endometrial adenocarcinoma. HER-2/neu oncogene expression is also a major prognostic factor in endometrial carcinoma, but positive peritoneal cytology influences survival only in the presence of extrauterine disease. Frozen-section diagnosis and curettings findings at the time of surgery identify poor prognostic factors, allowing limited surgery in patients without poor prognostic indicators. Finally, DNA ploidy as determined by flow cytometry was of prognostic value in uterine sarcomas in one study but not in another when endometrial stromal sarcomas were analysed separately.
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PMID:Pathological findings and prognosis from uterine malignancy. 840 44

HER-2/neu oncogene is believed to be involved in tumorigenesis of several human malignancies. To assess the pattern of expression of this oncogene in normal, hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to paraffin-embedded tissue sections obtained from 146 patients with endometrial adenocarcinoma. A spectrum of hyperplastic changes ranging from simple hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases. Expression for HER-2/neu oncogene was demonstrated as cell membrane staining. Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous expression for HER-2/neu oncogene. The intensity of the immunostaining and the number of cells stained for HER-2/neu oncogene had no significant association with surgical stage or histologic grade, although the proportion of patients demonstrating overexpression increased significantly as the histologic grade of their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a statistically significant correlation was found between the level of expression of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated that HER-2/neu oncogene expression is variably present in normal and hyperplastic endometrium. Association between HER-2/neu oncogene expression, higher grade lesions and poor survival in patients with endometrial cancer may also justify assessment of HER-2/neu oncogene as a reliable prognostic indicator.
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PMID:Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant endometrium. 964 53

The role of estrogen and estrogen-related growth factors in the mechanism of hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma cells (Ishikawa cells), which possess both estrogen and progesterone receptors, was optimally stimulated by 10 nM estradiol. Both transforming growth factor (TGF)-alpha and epidermal growth factor (EGF), added to the culture media, stimulated the proliferation of Ishikawa cells in a dose-dependent manner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of these cells. The production of TGF-alpha into culture media was 5-40 pg/10 cells/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estradiol increased the TGF-alpha production of Ishikawa cells by approximately 2.5-fold of the control level. In contrast, the production of TGF-alpha in hormone-unresponsive HEC-50 cels was not influenced by estradiol. C-erbB-2 oncoprotein expression of human endometrial adenocarcinoma cells, detected by both immunocytochemical staining and Western blot analysis, was associated with the tumor grade of the original tumor tissues. Ten nanomoles of estradiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incubation period of 72 h, whereas estradiol did not affect the expression in HEC-50 cells.
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PMID:Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells. 985

Previous studies of oncogenes, tumor suppressor genes, and proliferation markers in endometrial adenocarcinoma have obtained conflicting results regarding the usefulness of these markers in predicting prognosis. This study examined p53, PCNA, and c-erbB-2 immunohistochemically to clarify the relationship of these markers to each other and to FIGO stage, myometrial invasion, and survival. We studied 64 cases of endometrial carcinoma, treated between 1988 and 1995, for overexpression of p53, percentage of PCNA expression (PCNA index), and c-erbB-2 cytoplasmic membrane staining. Thirty-two percent of tumors expressed p53, 39% displayed a PCNA index of > = 25%, and 69% expressed c-erbB-2. p53 overexpression was significantly associated with stage (p=0.027), PCNA index > = 25% (p=0.005), c-erbB-2 expression (p=0.018), and vital status (p=0.04). PCNA index > = 25% was associated with stage (p=0.008), myometrial invasion (p=0.008), and c-erbB-2 expression (p=0.05), and weakly associated with vital status (p=0.07). No associations were observed for c-erbB-2 with stage, invasion, or vital status. There was some suggestion of a decreased survival in patients whose tumors overexpressed p53 (Log Rank; p=0.09) or had a PCNA index > = 25% (Log Rank; p=0.13). Additional, larger studies are needed to evaluate the prognostic value of PCNA and p53 expression in endometrial adenocarcinoma.
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PMID:Prognostic significance of p53, PCNA, and c-erbB-2 in endometrial enocarcinoma. 1042 71

This study investigated the relation between immunohistochemical prognostic factors and clinical stage and histopathological grade in endometrial adenocarcinoma. Twenty-seven patients with a mean age of 61 (38-74), who underwent radical surgery due to endometrial adenocarcinoma in our hospital between 1983-1998, were re-evaluated. For clinical staging FIGO criteria were used. Histopathological differentiation of the tumor was graded as good (grade 1), moderate (grade 2), and poor (grade 3). Estrogen and progesterone receptors, c-erb B2, UEA 1, Ki-67, PCNA and p53 were studied as immunohistochemical prognostic factors. There were no patients in stages IA and IIIB. Among the prognostic factors, PCNA was the most significantly stained marker, followed by c-erb B2, estrogen and progesterone receptors, regardless of the clinical stage and histopathological grade of the tumor. The least positivity was achieved with Ki-67. There was no significant difference when each prognostic factor was analysed with respect to clinical stage and histopathological grade. In our study no significant relation was found between the prognostic factors and the clinical stage and histopathological differentiation of the tumor. Therefore the cost effectiveness of the utilization of these factors should be reconsidered.
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PMID:The utilization of immunohistochemical prognostic factor in endometrial adenocarcinoma: is it cost effective? 1084 86

Endometrial adenocarcinoma is the most common pelvic genital malignancy in the western world. The most common subtype of endometrial cancer is endometrioid endometrial carcinoma (EEC), which has a relatively good prognosis. Uterine serous papillary carcinoma (USPC) is also a subtype of endometrial carcinoma. This is an aggressive carcinoma with the majority of patients presenting at stage 3-4 and has a worse prognosis stage for stage when compared with EEC. In addition, the treatment of USPC is more extensive than that of EEC, and therefore definitive diagnosis before surgery ensures the optimum management for the patient. This study aims to determine whether P53, C-erbB-2, and PTEN antibodies have a use in the diagnosis and distinction of these cancers. We created tissue microarrays for 35 cases of EEC and 25 cases of USPC, and then we assessed the immunohistochemical expression of P53, C-erbB-2, and PTEN. There was significantly greater expression of P53 in USPC than that in EEC. However, neither C-erbB-2 nor PTEN showed any significant difference in expression between the two carcinomas. P53 may have a role in the diagnosis of USPC, but neither C-erbB-2 nor PTEN would be useful as part of a diagnostic panel.
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PMID:The use of P53, PTEN, and C-erbB-2 to differentiate uterine serous papillary carcinoma from endometrioid endometrial carcinoma. 1536 Dec 7

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80


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