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)

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed immunohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti-p53 monoclonal antibody, PAb1801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c-erbB-2 protein (P less than 0.05), high histologic grade (P less than 0.01), advanced clinical stage (P less than 0.05), and negative estrogen receptor status (P less than 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival of patients (P less than 0.01). These results suggest that immunohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.
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PMID:Nuclear p53 immunoreaction associated with poor prognosis of breast cancer. 167 56

The emergence of resistant cells reduces the efficacy of many forms of drug therapy in human breast cancer. In order to understand some of the possible mechanisms by which hormonally dependent human breast cancers develop resistance to progestin therapy we have developed a human breast cancer cell line (5-RP) which is resistant to the growth inhibitory effects of progestins in culture. These cells routinely grow in 10 microM medroxyprogesterone acetate (MPA). The cell line was developed from T-47D-5 human breast cancer cells by stepwise selection in increasing concentrations of MPA. The progestin-resistant phenotype was relatively stable as assessed by the removal of MPA from the medium for varying periods of time. 5-RP cells passaged in the absence of MPA were still essentially insensitive to the growth inhibitory effects of MPA for at least 22 passages. Even at 53 passages out of the drug the 5-RP line was still less sensitive than the original T-47D-5 parent line. Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor mRNA were both increased in the 5-RP line compared to the T-47D-5. Consistent with increased TGF-alpha expression, the EGF receptor measured by ligand binding was decreased. When the cells were removed from MPA, TGF-alpha expression declined gradually, but EGF-receptor mRNA levels increased, as did EGF-binding activity. These cells remained estrogen and progesterone receptor positive. Although progestins did not downregulate estrogen receptor expression, they did downregulate progesterone receptor expression in the 5-RP line. The progesterone receptor level of the 5-RP line, in the absence of MPA, was approximately 58% of that found in T-47D-5 cells, even after MPA had been removed for long periods of time. This decrease in receptor level was reflected in decreased ability to respond to progestins as assessed by the decreased ability of MPA to activate expression of both an endogenous gene (EGF receptor) as well as a transiently transfected progestin-responsive gene (MMTV-TK-CAT). Progestin resistance in the 5-RP cell line appears to be multifactorial, involving both increased growth factor expression and decreased receptor levels. It is likely, however, that these two aspects do not account entirely for the progestin-resistant phenotype and as yet other unidentified mechanisms may also be involved.
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PMID:Mechanisms involved in the evolution of progestin resistance in human breast cancer cells. 184 41

Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HER-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10(-10) M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HER-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.
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PMID:Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines. 197 45

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, menopausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.
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PMID:Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status. 197 54

By immunohistochemical staining C-erbB-2 (neu) oncogene was found on the cell membrane in 19 out of 44 primary breast cancers from a pathology archive. No obvious relation was found between neu oncogene, age, and lymph node status and tumor size. There was a tendency towards smaller primary tumors and more estrogen receptor-negative tumors in the oncogene-positive group. No case of distant metastasis during follow-up was found among the oncogene-negative patients, while 6 oncogene-positive patients developed such metastases. This suggests that the neu oncogene is an independent prognostic factor, which might predict the development of distant metastasis. Further studies including more patients and long-term survival analysis are, however, needed in order to evaluate the prognostic significance of the neu oncogene.
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PMID:Neu (C-erbB-2) oncogene in breast cancer and its possible association with the risk of distant metastases. A retrospective study and review of literature. 197 48

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.
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PMID:c-erbB-2 protein expression in node negative breast cancer. 197 14

Recently cervical cancer is defined as a sexually-transmitted disease, and human papillomavirus (HPV) has been focused as one of its etiologic agents. It is known that cervical cancer is extraordinarily rare in non-human mammals that have the estrous cycle. In contrast, cervical cancer is frequent in human beings which have lost the estrous cycle, and subsequently evolved a sexual behavior irrespective of the menstrual phase. Therefore, upon the hypothesis that the estrous cycle is a period protected from a sexually transmitted disease, we studied the status of local defence mechanism and growth/differentiation of normal cervical epithelium during the menstrual cycle and pregnancy. Then, the influence of HPV-infection on the growth and differentiation of cervical epithelium was analyzed. As a local immune system of the cervix, both IgA and IgG are secreted in the cervical mucus, and the levels in the follicular phase were significantly higher than those during the luteal phase and pregnancy. An existence of local defence mechanism in the follicular phase is suggested. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasal cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk for HPV infection. As factors regulating growth and differentiation of cervical squamous epithelium, immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), c-erbB-2 protein, adult T-cell leukemia-derived factor (ADF), and HPV DNA was examined. In normal cervix, basal cells were usually ER-positive and PR-negative. Parabasal cells were ER-positive and PR-negative in the follicular phase, while they were ER-negative and PR-positive during the luteal phase and pregnancy. Considering the results of Ki-67 expression, the ER-negative and PR-positive status is possibly related to the proliferation of the cervical squamous epithelium. In cervical condylomas, basal cells infected by HPV6/11 were ER-positive, but HPV16/18-infected cells were ER-negative. Neoplastic cells of CINs and invasive squamous carcinomas containing HPV DNA 16/18 were ER-negative, while those containing HPV DNA 31/33/35 were weakly ER-positive. PR was positive in 2 of 2 condylomas, 18 of 26 CINs, and 13 of 22 invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on pathogenesis of cervical carcinoma based on the analysis of growth and differentiation mechanism of cervical epithelium]. 217 18

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

We have earlier described a monoclonal antibody (323/A3) against a Mr 43,000 surface glycoprotein of MCF-7 human breast cancer cells which shows considerable specificity for primary and metastatic breast tumors (Cancer Res., 46: 1306-1317, 1986). Here we report the occurrence of the 323/A3 antigen in a large cohort of primary breast tumors (m = 384) and its interrelationship with several clinically important variables. Frozen, stored tumor tissues were examined by a Western blot procedure, and the level of 323/A3 protein in individual tumors was calculated in arbitrary units based on the integrated Mr 43,000 signal in tumors compared with an MCF-7 internal standard. Thirty-six % (139 of 384) of tumors were found to be positive for 323/A3. Higher frequencies of 323/A3 protein were found in tumors larger than 2 cm (P = 0.03), tumors with infiltrated lymph nodes (P = 0.01), and tumors without estrogen receptor (P = 0.006). No significant relationship was found with patient age, menopausal status, or progesterone receptor status. Of the newer clinical determinants proliferative rate (% S phase), DNA ploidy, and the lysosomal protease cathepsin D, but not the HER-2/neu oncogene protein, were significantly correlated with 323/A3. The presence of 323/A3 protein was also related to increased recurrence (P = 0.003) and mortality (P = 0.036) after primary treatment. As an exposed surface antigen, this glycoprotein might be a useful target in radioimaging and immunotherapy of some human breast tumors, especially those having large size, infiltrated lymph nodes, deficient estrogen receptor, high proliferative rate, abnormal DNA content, and high levels of cathepsin D, all of which are ominous indicators of tumor behavior.
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PMID:Association of the 323/A3 surface glycoprotein with tumor characteristics and behavior in human breast cancer. 233 24

Two cell lines (University of Michigan squamous carcinoma of the vulva UM-SCV-1A and UM-SCV-1B) were established from the primary tumor and a malignant pleural effusion of a 62-year-old woman. Both tumor specimens grew vigorously in vitro and could be passaged after only 14 and 10 days in culture, respectively. Both cell lines undergo 3 population doublings in 4 days, reaching saturation densities of 5 x 10(5) cells/cm2, and have been carried through more than 30 in vitro passages. In nude mice the cultured cells initially formed tumors but these regressed 2-3 weeks after inoculation. The regressing mouse tumors consisted of poorly differentiated squamous carcinoma surrounded by an inflammatory lymphoid infiltrate. The UM-SCV-1 cell lines express membrane antigens typically displayed by squamous-cell carcinomas. These include the HLA class-1 light chain beta 2-microglobulin, pemphigus, pemphigoid, and the alpha 6 beta 4 integrin defined by the UM-A9 monoclonal antibody (MAb). In contrast to the A431 vulvar carcinoma, these tumor lines do not have amplified expression of the epidermal growth factor (EGF) receptor. Although tissue from the primary tumor contained low levels of estrogen receptor activity, no receptor activity was detected in the cell lines. Nevertheless, both lines were sensitive to growth inhibition by tamoxifen. This effect was not reversible by estradiol, indicating an estrogen-receptor-independent mechanism. The tumors were both hypotetraploid, contained the same chromosome rearrangements and had stable karyotypes in vitro. Each contained inv(1)(p36.3q32.1), del(4)(q12), dic(4;11)(q12;p11.2), i(5p), der(6)t(3;6)(q25.1;p21.1), several rearrangements involving chromosomes 8 and 14, + i(13), i(18p), a dicentric t(11;19), and 2 or 3 unidentified markers. Since the karyotypes of both tumors were the same, no major karyotypic change was associated with metastatic spread. These paired primary and metastatic SCC lines from an unusually aggressive vulvar carcinoma provide an in vitro model for analysis of the biological basis of this tumor's behavior.
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PMID:Phenotypic characterization, karyotype analysis and in vitro tamoxifen sensitivity of new ER-negative vulvar carcinoma cell lines, UM-SCV-1A and UM-SCV-1B. 233 95


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