UNIPROT:P10415 - FACTA Search

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Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent of apoptosis and the expression of Bcl-2 was investigated in tumor samples from 165 women who underwent surgery for primary breast carcinoma between 1989 and 1990 in South-East Sweden. Apoptosis was assessed by a DNA fragmentation assay for flow cytometry. Bcl-2 protein expression was analyzed with immunocytochemistry. Bcl-2 immunoreactivity correlated with estrogen receptor (ER) and progesterone receptor (PgR) positivity and was inversely correlated with p53 accumulation. Apoptosis increased with patient age and a high degree of apoptosis was negatively associated with Bcl-2 immunostaining. Apoptosis showed no significant correlation with any of the other variables studied, including prognosis. The group with Bcl-2-positive tumors tended to have a lower risk of distant recurrence than others, but the association of Bcl-2 with recurrence was different in groups divided by ER and PgR status. Whereas Bcl-2 positivity indicated a low recurrence rate among PgR-negative patients, in the PgR-positive group, those with Bcl-2-positive tumors showed a non significantly higher recurrence rate than Bcl-2-negative cases. In the PgR-positive group, Bcl-2-positive tumors also appeared more frequently to be lymph node positive and DNA aneuploid. The results suggest that hormone receptor status is of importance for the prognostic role of Bcl-2. Likewise, patient age merits consideration when apoptosis is studied in human cancer.
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PMID:Apoptosis and Bcl-2 expression in relation to age, tumor characteristics and prognosis in breast cancer. South-East Sweden Breast Cancer Group. 1039 27

Ninety-eight minimal breast cancers (MBCs) diagnosed between 1975 and 1990, and all originally considered to be invasive were found, on review, to form three groups: (a) 28 predominantly invasive carcinomas < or = 10 mm ('predominant invasive'); (b) 48 predominantly ductal carcinoma in situ (DCIS) lesions with definite foci of invasion each < or = 10 mm ('predominant DCIS'); and (c) 22 DCIS without evidence of invasion ('pure DCIS'). Tumour histology and immunohistochemical expression of Ki-67, c-erbB2, p53, oestrogen receptor (ER), progesterone receptor (PR), and Bcl-2 were compared. The major finding was the contrasting features in the two invasive groups, with significant differences in their extent of invasion (P < 0.0001), tumour grade (P = 0.03), DCIS type (P = 0.008) and in marker expression. In the predominant invasive group, the infiltrative component was usually greater than 5 mm, low-grade and associated with well-differentiated DCIS. Expression of Ki-67, c-erbB2 and p53 was generally low, and that of ER, PR and Bcl-2 high. The predominant DCIS group in contrast had a much smaller, commonly high-grade, invasive component, usually with poorly differentiated DCIS and the reverse pattern of marker expression. Although not significant, survival of patients in the predominant invasive group was slightly better. These findings suggest that invasive MBCs should perhaps be treated as separate entities, in order to aid more appropriate selection of treatment.
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PMID:Minimal breast cancer: evaluation of histology and biological marker expression. 1040 7

Many different pathological and biological variables which characterize breast carcinomas have been found to be associated. The aim of this work was to analyze the complex relationship among these parameters. The pathologic, biologic, and clinical characteristics of a series of primary breast carcinomas from 676 patients were retrospectively investigated. Multiple correspondence analysis of 13 factors revealed clustering of eight pathobiologic variables, that is histologic grade, necrosis, lymphoid infiltration, number of mitoses, c-erbB-2 overexpression, p53, progesterone receptor, and bcl2 expression. An index for each tumor calculated on the basis of these eight factors served to distinguish two different tumor phenotypes, designated A and B. Phenotype A is represented by tumors sharing most of the biologic features of normal breast tissues: indeed, these tumors are characterized by a relatively high degree of differentiation, low proliferation, no necrosis or leukocyte infiltration, and no gene alterations. By contrast, phenotype B is quite divergent from the normal tissue because of its poor differentiation, high proliferation, frequent gene alterations and evidence of a host immune reaction. As regards the disease progression, these two subsets showed marked differences: phenotype A tumors had a low recurrence rate per year that remained constant over time and affected more frequently elderly patients, whereas group B tumors showed high aggressivity in the first years after surgery followed by a low long-term recurrence rate and were more frequently seen in younger patients. These data suggest that breast carcinoma consists of two different subsets that can be identified on the basis of pathobiologic features.
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PMID:Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors. 1151 69

An association has been reported between consumption of a high soy diet and a low incidence of breast cancer within populations of Southeast Asia. Phytoestrogens present in soy act as partial estrogen agonists or antagonists and can inhibit breast cancer cell proliferation in vitro. The effect of 14-day dietary soy supplementation with 60 g (45 mg isoflavones) on the normal breast of 84 premenopausal patients was determined. Serum concentrations of the isoflavanoids, genistein, daidzein, and equol, were raised in patients after soy supplementation (P < or = 0.025). Nipple aspirate (NA) levels of genistein and daidzein were higher than paired serum levels, both before (P < 0.001 and P = 0.001, respectively) and after soy supplementation (P < 0.001 and P = 0.049, respectively); however, there was no significant increase in NA isoflavone levels in response to soy. NA levels of apolipoprotein D were significantly lowered and pS2 levels raised in response to soy supplementation (P < or = 0.002), indicative of an estrogenic stimulus. No effect of soy supplementation on breast epithelial cell proliferation, estrogen and progesterone receptor status, apoptosis, mitosis, or Bcl-2 expression was detected. In conclusion, short term dietary soy has a weak estrogenic response on the breast, as measured by nipple aspirate apolipoprotein D and pS2 expression. No antiestrogenic effect of soy on the breast was detected.
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PMID:Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. 1056 43

The differences in immunohistochemical expression of p53, bcl-2, bax, estrogen receptor (ER), and progesterone receptor (PR) were evaluated in 40 endometrioid and 21 papillary serous carcinomas of endometrium and correlated with known predictors of survival, such as grade and stage. Uterine papillary serous adenocarcinomas (UPSA) showed significantly higher p53 expression than did uterine endometrioid adenocarcinomas (UEA) (76.2% versus 35%), whereas both ER and PR were more often positive in endometrioid than in serous tumors (p = .005 and .0005). No significant difference was found in bcl-2 and bax expression between both histologic types. However, there was definite decrease in intensity of bcl-2 in UPSA compared with UEA. In endometrioid carcinoma, p53 overexpression was associated with high-grade and advanced-stage tumors (p = .0006 and .006), whereas ER and PR expression was associated with low-grade and early-stage tumors (p = .0006 and .0001; p = .003 and .0006). Bcl-2 immunopositivity was more common in low-grade, early-stage rather than in high-grade, advanced-stage adenocarcinomas, but the difference was not statistically significant (p = .24 and .07). Bax immunopositivity was associated with well-differentiated (p = .04) and early-stage tumors. Furthermore, a significant inverse relationship between bax and p53 reactivity was defined (p = .05), especially in tumors of endometrioid type. Bax and PR immunoexpression correlated near the limit of statistical significance (p = .08), whereas no relationship was found among bax, bcl-2, and ER immunopositivity. Our results indicate that the differences in immunohistochemical profiles of endometrioid and serous carcinomas support the existence of different molecular pathways of their development. The correlation of immunohistochemical findings with histologic grade and clinical stage could help in predicting biologic behavior and planning treatment in patients who are diagnosed as having these tumors.
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PMID:Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature. 1078 3

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS.
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PMID:Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers. 1138 66

The purpose of this study was to further investigate the role of estrogen but especially progesterone on epithelial ovarian tumor development since previous studies have suggested a relationship between serum progesterone, progesterone receptor expression and prognosis. Serum progesterone concentration, the immunohistochemical expression of estrogen receptor alpha (ER), progesterone receptor A/B (PR), Ki-67, Bcl-2, p53, apoptosis and morphology were determined in 33 patients, all with poorly differentiated surface epithelial ovarian tumors of different types. ER was expressed in 79% and PR in 33% of the tumors. This group of aggressive tumors was highly proliferative as indicated by Ki-67 index (mean 38.9%), and in some cases proliferation appeared to be mainly located to areas with a high ER density. The majority of cases (76%), both receptor-positive and -negative, overexpressed p53. High ER expression was related to a lower apoptotic activity as compared with tumors with a low expression of the ER (p = 0.008). Serum progesterone in itself did not show any clear relationship to steroid receptor status, expression of Ki-67, p53, Bcl-2 or signs of apoptosis. Survival in this small but homogeneous group of advanced epithelial ovarian cancers, showed an improved survival rate in patients with high serum progesterone, especially in combination with expression of progesterone receptors (p = 0.04). In conclusion, estrogen and progesterone receptors in parallel with deranged p53 and Ki-67 were expressed to a great extent. The finding of a lower apoptotic activity in tumors with a high expression of ER and an indication of increased proliferation in areas with high ER density gives a rationale for antiestrogen therapy even in poorly differentiated epithelial ovarian cancers. Improved survival is related to serum progesterone, especially in combination with PR expression.
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PMID:Steroid receptors and hormones in relation to cell proliferation and apoptosis in poorly differentiated epithelial ovarian tumors. 1140 19

The aim of this study was to analyse the relationships between the expression of c-erbB-2, estrogen receptor (ER), progesterone receptor (PR), Bcl-2 and PCNA in node negative breast cancer. Expression of these markers was determined by HercepTest, by immunohistochemistry and quantified by morphometry in the group of 125 selected breast carcinoma patients with broad spectrum of histological types and grades. Multivariate statistical analysis revealed only relationships between ER/PR, ER/Bcl-2, ER/grade and ER/age. There was not found any significant relationship between c-erbB-2 expression and any other immunohistochemical marker, apocrine metaplasia, histological type or patient characteristics. The same result was found in complete group of tumors as well as in individual groups divided according to histological type. These results indicate that in node negative breast tumors, c-erbB-2 expression does not correlate inversely with hormone receptor status and hormone responsiveness like previously reported metastasising breast cancer and that the prognostic significance of c-erbB-2 expression in these tumors is not clear.
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PMID:Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. 1208 2

Loss of estrogen-responsiveness and impaired E-cadherin expression/function has been linked to increased metastatic potential of breast cancer cells. In this study, we report that proliferation of breast cancer cells can resume following removal of a toxic stimulus causing severe impairment of cell adhesion and estrogen responsiveness. This type of response was induced by okadaic acid (OA) in MCF-7 cells, and was accompanied by an almost complete block of DNA synthesis, loss of cell-cell contact and cell detachment from culture dishes, loss of estrogen receptor (ER), progesterone receptor (PR) and E-cadherin, whereas only a weak, if any, inhibition of protein synthesis could be observed. These responses were detected in MCF-7 cells after a 1-day treatment with 50 nM OA, and could be reversed if OA-treated cells were recovered in a culture medium devoid of the toxin, so that rescued cells resumed growth 8-12 days after replating. By pulse-chase experiments, we found that protein synthesis was not significantly affected in rescued cells, whose DNA synthesis, instead, was almost completely blocked during the first days of MCF-7 cell rescue from OA treatment. We also analyzed E-cadherin, mitogen activated protein kinase isoforms ERK1 and ERK2, Bcl-2 and BAX proteins during the rescue of MCF-7 cells from OA-induced cell death, and found that their expression followed temporally defined patterns. Cellular levels of E-cadherin returned to control levels within the first days of the rescue, followed by ER, ERK1, and ERK2, and finally by Bcl-2 and BAX proteins. Under our experimental conditions, restoration of cell adhesion did not require a functional ER system, but recovery of a normal ER pool accompanied resumption of estrogen-dependent proliferation of OA-treated MCF-7 cells.
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PMID:Recovery of cellular E-cadherin precedes replenishment of estrogen receptor and estrogen-dependent proliferation of breast cancer cells rescued from a death stimulus. 1211 23

In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.
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PMID:Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis. 1216 Mar 27

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