Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of recombinant gamma interferon (IFN gamma) on proliferation, estrogen-receptor (ER) content, mRNA level and protein secretion of a breast cancer estrogen-induced protein pS2/BCEI were investigated in two human breast cancer cell lines, ZR75-1 and T47D. Both cell lines have estrogen and progesterone receptors and previously showed HLA class I and class II responses to IFN gamma (Int J Cancer 1990; 45: 1169). An antiproliferative effect of IFN gamma (1000-5000 U/ml) was observed in serum containing medium on ZR75-1 but not on T47D cells. Noninhibitory concentration of IFN gamma (100 U/ml) had sensitising antiproliferative effect with antiestrogens on ZR75-1 cells whereas IFN gamma did not modify the growth inhibition observed in T47D cells with antiestrogens. In serum-free, estradiol-free, phenol-red-free chemically defined medium (Cancer Res 1984; 44: 4553), IFN gamma abolished in ZR75-1 but not in T47D the 30% growth stimulation induced by estradiol. In ZR75-1 cells, IFN gamma induced a transitory 30-50% increase of ER content, as measured by ER-enzymoimmunoassay, at day 2 of culture, and reduced mRNA level and secretion of pS2/BCEI. In T47D cells, a 30-50% decrease of ER content was observed but only when cells were long term cultured (30 weeks) with IFN gamma. In this cell line, no transcription of pS2/BCEI was observed. Antiproliferative action of IFN gamma on ZR75-1 cells is associated with an inhibition of estradiol effects and a reduction of pS2/BCEI mRNA level and protein secretion.
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PMID:Modulation of proliferation, estradiol receptors and estrogen regulated protein PS2/BCEI in human breast cancer cell lines by gamma interferon. 176 58

Expression of the pancreatic spasmolytic peptide (hSP) gene and pS2 (a gene isolated from oestrogen-induced breast carcinoma cells) were analysed in 36 samples of human stomach carcinoma. 17 tumours were investigated at the RNA level (by northern blots) as well as at the gene product level (by immunochemistry). Since pS2 had been shown to be expressed in normal stomach mucosa its activity in carcinoma samples was expected. Surprisingly, strong pS2 immunoreactivity was noted in the diffuse carcinoma type, whereas the intestinal type displayed weak reactivity. The tumour samples showing strong immunostaining expressed the regular 0.6 kb pS2 RNA band and weak staining was paralleled by aberrant transcripts. Additionally, only in tumour samples with regular pS2 transcription was the typical 0.7 kb hSP RNA band seen; samples with aberrant pS2 bands did not express hSP at all. This is the first demonstration of hSP gene activity in a human tumour.
Eur J Cancer 1991
PMID:Expression of the breast cancer associated gene pS2 and the pancreatic spasmolytic polypeptide gene (hSP) in diffuse type of stomach carcinoma. 182 22

Expression of the oestrogen-regulated pNR-2/pS2 protein has been studied in paraffin sections of a series of 172 primary breast cancers using an immunohistochemical technique. Positive staining of tumour cells was found in 117 tumours (68%): most of these tumours contained only a small proportion of positive cells. pNR-2 immunohistochemical staining correlated positively and significantly with the presence of oestrogen receptor. Mean percentages of pNR-2 positive cells were lower in tumours from postmenopausal women. Smaller, better differentiated tumours were significantly more likely to stain positively for pNR-2. The percentages of pNR-2 positive tumour cells in primary tumours and synchronously excised lymph node metastases were very similar. pNR-2 expression showed an unexpected positive association with lymph node metastasis. We were unable to find any significant association between pNR-2 immunohistochemical staining and either time to relapse or overall survival. There was a significant association between pNR-2 expression in primary tumours and response to endocrine therapy on relapse: positive pNR-2 immunohistochemical staining in primary tumours is predictive of response to hormonal therapy on relapse.
Br J Cancer 1991 Apr
PMID:pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response. 185 Jun 11

In search of critical genes in the mechanism of estrogen action in human breast cancer, we previously showed that estrogen stimulates transcription of the c-myc gene in estrogen-dependent (MCF-7) cells. We have now examined the role of c-myc in estrogen-stimulated growth of MCF-7 cells through the use of a synthetic antisense c-myc phosphorothioate oligonucleotide to specifically inhibit expression of the c-myc protein. Estrogen induces a 5-fold increase in c-myc protein expression within 90 min in steroid-deprived cells, as detected by Western blot. Prior exposure of MCF-7 cells to 10 microM c-myc antisense oligonucleotide results in up to 95% inhibition of the c-myc protein expression induced by estrogen. Antisense-myc oligonucleotide inhibits estrogen-stimulated cell growth by up to 75% over 9 days and also exerts a cytostatic effect on the growth of estrogen-independent MDA-MB-231 cells which show relatively high, constitutive expression of c-myc. Sense-myc and antisense-pS2 oligonucleotides have no effect on c-myc protein level or growth in either cell line. These results demonstrate both the specific and durable effects of antisense phosphorothioate oligonucleotides. Furthermore, these results indicate a critical role for c-myc in the growth of breast cancer cells and support the hypothesis that loss of estrogen regulation of this gene may be an important factor in the progression of breast cancer.
Cancer Res 1991 Aug 01
PMID:Inhibition of c-myc expression by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer. 185 15

To study the mechanism of regression of human mammary cancer following estrogen ablation, estrogen-responsive MCF-7 human mammary adenocarcinoma cells were inoculated into ovariectomized female nude mice supplemented with exogenous 17 beta-estradiol (E2) via an E2 implant. Implants were then removed when MCF-7 tumors were 400 mm3 in size. Removal of the E2 implants resulted in a 50% tumor regression by 2 weeks following E2 ablation. Associated with this regression is a rapid (i.e., within 1 day following E2 ablation) enhanced expression of the transforming growth factor beta 1 and TRPM-2-genes, two genes the expression of which has been previously demonstrated to be enhanced in a variety of cell types induced to undergo programmed cell death (i.e., apoptosis). The enhanced expression of transforming growth factor beta 1 and TRPM-2 is not a nonspecific response since the expression of other genes, like c-fos, c-H-ras, and pS2, decrease following E2 ablation. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that precede the dramatic reduction in tumor volume following E2 ablation. These results demonstrate that the regression of MCF-7 human mammary cancers in nude mice following estrogen ablation is due to a sequence of biochemical and morphological changes that result in both the cessation of cell proliferation and activation of programmed death or apoptosis of these MCF-7 cancer cells. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even estrogen-independent human mammary cancer cells.
Cancer Res 1991 Jan 01
PMID:Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. 189 37

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 nM) produce a marked reduction in the growth, measured by thymidine uptake, of MCF-7 cells in full growth medium, but had only a small effect on MDA-MB-231 and T47D cells. Bryostatin alone also inhibited growth but to a lesser extent than seen with TPA. The effect of TPA on MCF-7 cells was partially reversed by bryostatin, added simultaneously or after TPA, suggesting bryostatin does not simply mimic TPA in this system. Even though both are believed to act via effects on protein kinase C, bryostatin appears to act as antagonist to the effect of TPA as well as a partial agonist on its own. When the oestrogen receptor positive MCF-7 and T47D cells were maintained in charcoal stripped serum, the increase in DNA synthesis on stimulation with oestradiol was inhibited with 50 nM TPA in MCF-7 cells but not in T47D cells. The effects of these treatments on the expression of two well characterised oestrogen responsive genes pNR2(pS2) and pNR100 (Cathepsin-D) were examined. Rather than preventing transcription of these oestrogen responsive genes, TPA alone increased pNR2 and pNR100 levels in MCF-7 cells and the combined effect of oestradiol and TPA had a marked synergistic effect in increasing the transcript levels of these genes. In T47D cells pNR2 transcripts were not detected and the increase in pNR100 mRNA levels were not affected by TPA. We conclude that the inhibitory effects of TPA on the growth stimulation of MCF-7 cells by oestradiol was not due to a general inhibition of the expression of oestrogen responsive genes. An alternative possibility examined was that the growth inhibitory effect of TPA on MCF-7 cells might be due to stimulation of TGF-beta 1, acting as an autocrine inhibitory growth factor. Oestradiol treatment of MCF-7 cells reduced the levels of TGF-beta 1 mRNA whereas TPA produced a marked increase. The combined effect of TPA and oestradiol further increased TGF-beta 1 mRNA above the levels seen with TPA alone. Bryostatin had little effect on TGF-beta 1 expression either alone or in combination with oestradiol. These observations are consistent with the hypothesis that the inhibitory effect of TPA on MCF-7 cells may be partly due to autocrine inhibition by TGF-beta 1.
Br J Cancer 1991 Oct
PMID:Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells. 191 Dec 15

The pNR-2/pS2 protein is regulated by oestrogens in breast cancer cell lines. This report describes a systematic survey of pNR-2/pS2 expression in a number of common epithelial tumours. Expression was evaluated immunohistochemically in an archival series using antisera raised against the C-terminus of the pNR-2/pS2 protein. Expression of pNR-2/pS2 by malignant epithelial tumours was widespread. Intense immunohistochemical staining was found in tumour cells in a proportion of pancreatic (6/8), large intestinal (7/12), gastric (9/16) and endometrial (4/12) carcinomas. Positive staining for the pNR-2/pS2 protein was also found in both benign and malignant ovarian epithelial tumours and was very significantly associated with mucinous differentiation (P less than 0.00001). Small numbers of carcinomas of bladder (2/10) and prostate (2/7) showed less intense staining and single examples of cervical carcinoma (1/7) and lung carcinoma (1/19) stained positively. None of the renal carcinomas (0/16) examined stained positively. Positive staining showed no correlation with gender. Although there are reports of oestrogen receptor expression in most of the tumour types considered, the possibility of other regulatory influences must also be considered. The pNR-2/pS2 protein may well have a more general role in human epithelial neoplasia than hitherto realised.
Br J Cancer 1991 Oct
PMID:Expression of the pNR-2/pS2 protein in diverse human epithelial tumours. 191 Dec 16

Seventy-two patients with advanced breast carcinoma (42% bone, 25% visceral, 5.5% soft tissue, and 27.5% multiple site metastases) were evaluated to determine the relationship between tumor expression of the estrogen-regulated protein pS2, estrogen receptor (ER) or progesterone receptor (PgR) content, and response to hormonal therapy. Twenty-nine % of tumors were pS2 positive, 64% were ER positive, and 29% were PgR positive. Of the ER-positive patients (n = 43), 15 (35%) had greater than 10% of the invasive carcinoma which immunostained for pS2 (these were considered pS2 positive). Only 3 of 24 ER-negative tumors were pS2 positive. A weak association between pS2 expression and ER content (P = 0.08) but not PgR content was observed. Of pS2-positive patients, 52% had a partial or complete response to hormonal therapy. In 24% of pS2-positive patients the disease stabilized with treatment. In contrast, 27% of pS2-negative patients had a partial or complete response. In 10% of these patients the disease stabilized. Similar associations between therapeutic response and ER or PgR were not observed. The odds of having a clinical response to hormonal therapy was greater for pS2-positive than for ER- or PgR-positive tumors. pS2 expression may define a subset of ER-positive tumors that are more likely to respond to hormonal treatment.
Cancer Res 1991 Jan 15
PMID:pS2 expression and response to hormonal therapy in patients with advanced breast cancer. 198 78

Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.
J Natl Cancer Inst 1991 Feb 06
PMID:Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations. 198 96

The pNR-2 mRNA is regulated by oestrogens in cell lines established from metastatic human breast cancer cells. The levels of the pNR-2 and oestrogen receptor RNAs have been measured in 96 tumour samples from patients undergoing surgery for breast cancer. Oestrogen receptor mRNA was detected in 90% of the 60 primary breast tumour samples from patients not receiving endocrine therapy at the time of surgery, whereas the pNR-2 RNA was detected in 57%. In primary tumours the expression of pNR-2 was entirely dependent upon oestrogen receptor RNA expression. When the 60 primary tumours were considered, pNR-2 and oestrogen receptor mRNA levels were significantly correlated. There was no significant correlation for pNR-2 positive tumours. pNR-2 mRNA levels were similar in tumours of pre- and post-menopausal patients and were independent of tumour differentiation and nodal status. Oestrogen receptor and pNR-2 mRNA levels were also measured in 21 tumour samples from patients receiving primary tamoxifen therapy. Eleven of these had shown an objective response and a significantly larger number of tumours from these patients contained pNR-2 mRNA than from patients who did not respond (chi 2 = 6.08, P less than 0.025).
Br J Cancer 1990 Jan
PMID:Expression of the oestrogen regulated pNR-2 mRNA in human breast cancer: relation to oestrogen receptor mRNA levels and response to tamoxifen therapy. 215 95


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