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)

When deprived of steroid in the long term, T-47-D human breast cancer cells lose estrogen sensitivity of cell growth. This loss of response results from an increased basal growth rate in the absence of steroid, not from a loss of estrogen-stimulated growth, and it occurs without any loss of estrogen receptor number or function. Growth factor gene expression and sensitivity have been investigated in this model system in an attempt to unravel the molecular mechanisms underlying the progression to steroid autonomy. The transition was accompanied by a decreased dependence on added serum and by a loss of the stimulatory effects of insulin and basic fibroblast growth factor, but also by an acquired sensitivity to stimulation by transforming growth factor-beta (TGF-beta). An increase in TGF-beta 1 mRNA was detected following loss of steroid sensitivity. There was no increase in epidermal growth factor (EGF) receptor number. These findings are discussed in relation to current knowledge concerning the mechanisms by which estrogens stimulate breast cancer cell proliferation.
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PMID:Interaction of growth factors during progression towards steroid independence in T-47-D human breast cancer cells. 219 68

The effects of the tumor promoter phorbol 12-tetradecanoate 13-acetate (TPA) on the epidermal growth factor (EGF) receptor levels were investigated in hormone-dependent (MCF-7, T-47-D, and ZR-75-1) and hormone-independent (MDA-MB-231, HBL-100, and BT-20) human mammary carcinoma cell lines. In the absence of TPA, hormone-independent cell lines contained high concentrations of low-affinity EGF receptors (apparent Kd = 8 X 10(-10) M), whereas hormone-dependent cell lines exhibited low concentrations of high-affinity receptors (apparent Kd = 1 X 10(-10) M). TPA causes a change of the receptor from a high- to the low-affinity state in hormone-dependent cell lines (MCF-7, T-47-D, and ZR-75-1), as well as in the hormone-independent HBL-100, whereas the affinity remained unchanged in MDA-MB-231 and BT-20 cells. In addition, progesterone receptor levels are decreased after TPA treatment in the hormone-dependent cell lines MCF-7, T-47-D, and ZR-75-1, whereas the estrogen receptor levels remained unchanged. Tumor promoters such as TPA or teleocidin inhibited the proliferation of these cell lines at concentrations above 10 microM with the exception of the T-47-D cells. The most sensitive cell line towards growth inhibition by tumor promoter was the hormone-dependent MCF-7 cell line. Evaluation of different TPA analogs indicated a positive correlation between the growth-inhibitory effects and their ability to stimulate the subcellular redistribution of protein kinase C activity in MCF-7 cells. These data suggest a protein kinase C-mediated down-regulation of the progesterone receptor concentration and of the EGF receptor affinity, which is supposed to mediate the mitogenic response. Furthermore, these results support the hypothesis that the tumor-derived growth factors induced by estradiol act via the EGF receptor in hormone-dependent mammary carcinoma cells.
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PMID:Correlation between hormone dependency and the regulation of epidermal growth factor receptor by tumor promoters in human mammary carcinoma cells. 300 36

An immunohistochemical study was performed with 130 primary malignant human tumors of breast (n = 55)..colon/rectum (n = 16), stomach (n = 19), esophagus (n = 14), lung (n = 15) and liver (n = 11) using the 21N c-erbB-2 specific monoclonal antibody to identify the tumors that over-expressed the c-erbB-2 oncoprotein. Positivity appeared as an intense brown granular staining located predominantly at the cell membrane. This occurred in 41.8% of breast carcinomas, 12.5% of colorectal adenocarcinomas. None of the gastric adenocarcinomas, squamous cell carcinomas of the esophagus, small cell lung carcinomas or hepatocellular carcinomas were positive for the oncoprotein. The result of this study suggests that over-expression of the c-erbB-2 oncoprotein is common in breast cancer and relatively rare in other malignancies examined.
Asian Pac J Allergy Immunol 1993 Dec
PMID:Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study. 791 4

An immunohistochemical (IHC) study of the c-erbB-2 protein was performed in paraffin-embedded tissues from 506 primary breast carcinomas. An overexpression of c-erbB-2 was detected in 32% of the tumors and was correlated with a negative estrogen receptor status, increasing tumor size as well as axillary lymph node involvement. The five-year disease free survival was analyzed in 183 patients who have been followed for at least five years. No statistically significant association of c-erbB-2 status with survival was shown. However, longer survival in women over 50 years compared to under 50 years of age was detected among the c-erbB-2 positive patients. In the multivariate Cox's regression analysis, lymph node and vascular invasions were independent prognostic indicators among these patients. But c-erbB-2 status and other factors did not predict the relapse of breast cancer. However, these data may not negate the benefit of c-erbB-2 detected by IHC for identification of patients who have a poor prognosis and require more aggressive adjuvant therapy. Further studies in a larger group of patients with longer follow-up time may provide more valid information.
Asian Pac J Allergy Immunol 2001 Sep
PMID:Immunohistochemical study of c-erbB-2 expression in primary breast cancer. 1182 15

The estrogen receptor (ER)-alpha protein and ER mRNA were measured in 314 primary breast cancer patients by enzyme immunoassay (EIA) and reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. The positivity of ER protein was 53% while of ER mRNA was 37.6%. A significant positive association between ER phenotype and ER mRNA was observed (r = 0.40, p < 0.0001) with a positive-negative agreement between them of 71.8%. The percentage of ER-negative, progesterone receptor (PR)-positive breast tumors was 1.9% by EIA and 7% by RT-PCR assay. This may indicate a difference in ER variants in these studied patients. The ER protein and ER mRNA status were inversely related to tumor size and p53 positivity. Also, ER protein was frequently positive in patients with a higher number of lymph node invasions, well to moderate nuclear differentiated tumor cells and negative c-erbB-2 status. The difference of the ER or ER mRNA status regarding ages, menopausal status, tumor stages and histological types was not shown. In the present study, ER mRNA did not demonstrate a closer relationship to prognostic indicators of breast cancer than ER protein. Before including the ER mRNA assessment in routine investigations of breast cancer, its relationship to prognostic factors and survival outcome should be further assessed with a higher number of patients and a longer follow-up time.
Asian Pac J Allergy Immunol 2002 Mar
PMID:Estrogen receptor-alpha mRNA in primary breast cancer: relationship to estrogen and progesterone receptor proteins and other prognostic factors. 1212 13

A total of 74 patients with apparent early stage epithelial ovarian cancer who underwent exploratory laparotomy at King Chulalongkorn Memorial Hospital or other hospitals and were referred for further treatment, were evaluated. Formalin fixed paraffin-embedded ovarian tissue specimens were collected and immuno-stained with HER-2/neu antibodies for comparison with clinicopathologic data after median follow up of 46 months (range 3 - 83 months). The prevalence of HER-2/neu overexpression in these patients was 10.2%. No significant correlation between HER-2/neu overexpression and clinicopathological parameters (stage, ascites, capsular rupture, capsular adherence, histological subtype and histological grade) was found. Disease free survival and overall survival did not statistically differ between those with lesions positive or negative for HER-2/neu overexpression.
Asian Pac J Cancer Prev
PMID:Lack of prognostic significance of HER-2/neu in early epithelial ovarian cancer. 1826 Jul 19

Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic indicator in breast carcinoma in the local population.
Asian Pac J Cancer Prev
PMID:C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre. 1927 45

HER-2/neu has been found to be amplified or overexpressed in about 20-30% of breast cancers, in association with negative prognosticators and shortened survival. Determination of HER-2/neu status in breast-cancer patients, to select for adjuvant treatment with trastuzumab, is becoming standard breast-cancer clinical practice. This study aimed to investigate HER-2/neu status in breast-cancer by real-time quantitative polymerase chain reaction (PCR), allowing accurate and precise quantification of HER-2/neu amplification in tumor tissues. We evaluated 112 breast-cancer samples, of which 42 (37.5%) had HER-2/neu amplification. After a mean follow-up period of 71 months, HER-2/neu amplification was found to be significantly associated with increased risk of death (HR = 6.367, 95% CI = 1.787-22.684), even after adjusting for age, clinical stage, tumor size, lymph-node status, and histologic grade. These findings support a negative prognostic role for HER-2/neu in breast-cancer survival. We suggest that real-time quantitative PCR analysis of HER-2/neu amplification represents an alternative technique for establishing HER-2/neu status in routine clinical practice.
Asian Pac J Cancer Prev 2011
PMID:Her-2/neu amplification determined by real-time quantitative PCR and its association with clinical outcome of breast cancer in Thailand. 2212 48

Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone metastasis.
Asian Pac J Cancer Prev 2012
PMID:Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population. 2263 75

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.
Asian Pac J Cancer Prev 2012
PMID:Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors. 2309 83


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