Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The absence of estrogen receptors (ER) in human breast tumors has been associated with a poorer prognosis compared to patients with ER positive breast cancer. Previous studies from our laboratory have shown that a multidrug resistant human breast cancer cell line selected for resistance to Adriamycin (ADR) exhibited markedly increased expression of both the pi class glutathione S-transferase (GST-pi) and the selenium-dependent glutathione peroxidase. These studies also revealed that the ER status was inversely related to the expression of GST-pi in six human breast cancer cell lines and primary tumor specimens. In the present study, we have examined the relationship between ER status and several biological properties of these cells, including their levels of glutathione peroxidase (GSH-Px) and catalase expression, their capacity to generate toxic hydroxyl radicals (degrees OH) by redox cycling of ADR, and their sensitivities to the cytotoxic effects of ADR and the oxidant, H2O2. Our results show that expression of GSH-Px, but not catalase, is inversely related to the ER status in these cell lines. Formation of the degree OH induced by treatment of cells with ADR was inversely proportional to the GSH-Px activity in these cell lines, and thus directly related to the ER status. Sensitivity of these cells to ADR or to H2O2, however, was not consistently related to ER status, GSH-Px, or catalase activity, or to ADR induced degree OH radical formation. These results indicate that these parameters are not predictive of cellular susceptibility to oxidative damage in these cell lines under the conditions studied.
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PMID:Selenium-dependent glutathione peroxidase expression is inversely related to estrogen receptor content of human breast cancer cells. 165 87

Glutathione transferase (GST) activity and GST isoenzyme composition have been determined for 24 human neoplasms and 6 human tumor cell lines. Substantial activity (40-1010 milliunits/mg protein) was identified in all tumor specimens examined and three of the tumor cell lines. Three tumor cell lines, the human small cell carcinoma line SW2-10S, the Burkitt's lymphoma derived cell line Raji, and the human breast carcinoma cell line MCF-7, contained minimal GST activity. Although the small size of the tumor samples precluded isoenzyme analysis by substrate specificities, analysis of GST activity following sample separation by isoelectric focusing indicated that the predominant (comprising at least 70% of the 1-chloro-2,4-dinitrobenzene-conjugating activity) GST isoenzyme in each of these primary tumor (17 of 17) and tumor cell line (3 of 3) extracts was anionic (isoelectric point, 4.5-4.8). In three tumor samples, adenocarcinomas of the lung, colon, and stomach, analysis by isoelectric focusing identified minor but detectable (10-20% of total) cationic GST. The anionic form of GST has been purified to homogeneity from three primary human tumors: a malignant melanoma; a mesothelioma; and a breast carcinoma. GST from these tumors consists of two subunits each of Mr 25,200. On Western blot analysis, antibodies raised against the anionic GST purified from mesothelioma detect protein of Mr approximately 25,000 in extracts of both normal kidney and tumors containing anionic GST activity but not in extracts of human liver that did not contain detectable anionic activity. The amino acid compositions of these proteins were quite similar to that previously described for GST-pi and the amino-terminal amino acid sequences for these tumor-derived isoenzymes are identical to one another and to that previously described for GST-pi from human placenta. GST is a major enzymatic activity in many human malignancies, comprising as much as 3% of the cytosolic protein of some tumors. Anionic GST is the predominant form of glutathione transferase activity in many human tumors and human tumor cell lines. In selected tumor samples the predominant anionic GST isoenzyme has been identified as a member of the pi class of this enzyme family. In addition, at least 3 of 17 tumor samples contained lesser but detectable amounts of cationic GST, probably of the alpha class. By conjugating glutathione with electrophilic anticancer drugs, the substantial levels of GST in human tumors may have a role in the innate or acquired resistance of these neoplasms to anticancer therapy.
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PMID:Identification of an anionic form of glutathione transferase present in many human tumors and human tumor cell lines. 327 99

Rat hepatocellular carcinomas and normal liver have been screened for mRNA sequences which are more abundant in the carcinomas than in livers. The screen was done by differential colony hybridization of a cDNA library constructed from the mRNA of a primary tumor induced by diethylnitrosamine (DEN). One cDNA was isolated which hybridizes to a 900 nucleotide mRNA present in abundance in six chemically induced rat hepatomas (both primary and transplantable), but is not detectable in normal adult or fetal (17 day) liver. The nucleotide sequence of this cDNA is identical to that reported by Suguoka et al. for the placental isoenzyme of rat glutathione S-transferase (GST-P) (Nucleic Acids Res. 13:6049). A comparison of the GST-P amino acid sequence with those of two liver GST isoenzymes (Yal and Yc) shows only 26% overall homology; however, this homology is concentrated in three regions of 50%, 68.2% and 34.5%. Genomic blotting experiments show that the overproduction of GST-P mRNA in three Morris hepatomas is not due to amplification of genomic DNA sequences hybridizing with the GST-P cDNA. However, hybridizing sequences are contained on at least 72 kb of genomic DNA, suggesting great complexity of the rat GST-P locus.
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PMID:Cloning of a cDNA encoding the rat placental glutathione S-transferase: overproduction of the mRNA in hepatocellular carcinomas. 379 60

Markers of chemoresistance have been rarely investigated in human ovarian cancer. This study evaluates the clinical value in ovarian cancer of metallothionein (MT), heat-shock protein-27 (HSP-27) and glutathione-S-transferase pi and alpha (GST pi, GST alpha), recognized for their relation with drug resistance in vitro. The expression of these markers was evaluated by immunohistochemistry on paraffin-embedded tumor specimens from 86 patients with ovarian carcinomas diagnosed between 1977 and 1990 who received chemotherapy. Response to chemotherapy was evaluated using well-defined criteria. Marker expression was evaluated on a section of the primary tumor (81 cases) and, when available, on a section of tumor following chemotherapy (48 cases). MT was expressed in 38.3% of primary tumors unexposed to chemotherapy, HSP-27 in 50.6%, GST pi in 37%, and GST alpha in 50.6%. The expression of all four markers did not help to predict chemoresistance. The concordance between marker expression by the tumor before and after chemotherapy was weak (concordance, 51.2%-70.7%). Immunostaining was not associated (p > 0.1) with any prognostic factor such as stage, residual tumor after surgery and grade. Ovarian cancer is a highly heterogeneous neoplasm and the expression of markers of chemoresistance reflects this heterogeneity. Our data suggest that chemoresistance is more likely multifactorial and confirms the complexity of the in vivo model.
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PMID:Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases. 885 47

Glutathione S-transferase pi (GST-pi), a Phase II detoxification enzyme, has recently been implicated in protection against apoptosis. Expression of GST-pi and Bcl-2 protein, an established apoptosis marker, was analyzed by immunohistochemistry in 116 cases of infiltrative ductal breast carcinomas in Singapore women. The markers were correlated with apoptosis detected by the TUNEL method and clinico-pathological parameters. There were 67 (58%) GST-pi-positive breast tumors and 43 (37%) Bcl-2-positive tumors. In a large proportion of GST-pi-positive/Bcl-2-positive tumors, there was a distinct accumulation of the GST-pi enzyme within the nucleus of cancer cells when examined by double immunofluorescence labeling under confocal microscopy. GST-pi immunoreactivity was not significantly correlated with any of the traditional histologic factors known to influence prognosis, whereas Bcl-2 overexpression was associated with reduced size of primary tumor (P =.021) and positive estrogen receptor status (P =.001). Univariate analysis revealed that GST-pi-positive, Bcl-2-positive, and lower histological grade tumors had decreased levels of apoptosis (P =.024, P =.011, and P =.029, respectively). However, multivariate analysis showed that histological grade and Bcl-2, but not GST-pi, immunoreactivity were correlated with apoptotic status. The Kaplan-Meier disease-free survival curves showed a significant difference between GST-pi-positive and GST-pi-negative breast cancer cases (P =.002). Disease-free survival in patients with GST-pi-positive tumors was also worse than that in patients with GST-pi-negative tumors in the group who had adjuvant chemotherapy (P =.04). In patients who were lymph node positive, GST-pi immunopositivity was found to influence disease-free survival. Recurrence of tumors was also significantly affected by GST-pi immunoreactivity (relative risk of 8.1). The findings indicate that GST-pi-positive tumors are more aggressive and have a poorer prognosis than do corresponding GST-pi-negative breast cancers.
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PMID:Prognostic significance of glutathione S-transferase-pi in invasive breast cancer. 1280 61

The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.
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PMID:TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy. 1805 29