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)

Several vectors were used to express the complementary DNA for breast cancer estrogen-induced protein BCEI (also called pS2) in Escherichia coli. The best results were obtained by using the pUR 290 expression vector after deletion of the sequence encoding the signal peptide of the protein. In these conditions, beta-galactosidase-BCEI/pS2 fusion protein accounted for approximately 20% of total proteins in bacterial extracts. It was purified by chromatography on DEAE-Trisacryl or by gel electrophoresis and electroelution. Polyclonal antibodies were obtained by immunization of rabbits and goats, and monoclonal antibodies were raised in mice. Two types of monoclonal antibodies were obtained: one class recognized the native protein and was very efficient for the immunoprecipitation and immunopurification of the protein from breast cancer cells; a second class recognized the denatured protein and was especially effective for immunoblot studies. BCEI/pS2 could be detected by immunocytochemistry in breast cancer biopsies using monoclonal antibodies on frozen or paraffin-embedded sections. One of the antibodies (mBCEI11) exhibited high affinity for the protein and could be used at 1.9 micrograms/ml concentration for immunolabeling of histological sections. The mBCEI11 antibody was used in immunoaffinity chromatography to purify the peptide in a single step from culture media of estrogen-treated MCF-7 cells.
Cancer Res 1990 Apr 15
PMID:Monoclonal antibodies against native ant denatured forms of estrogen-induced breast cancer protein (BCEI/pS2) obtained by expression in Escherichia coli. 218 May 69

Previous articles have reported that the c-myb proto-oncogene was activated in various types of tumours of the hematopoietic system suggesting that this gene plays a role in the development of these malignancies. However no studies of the c-myb gene have as yet been performed in solid primary tumours. In the present study we have analysed in breast cancer the c-myb gene with the aim to determine its involvement in tumour progression. Expression of the c-myb oncogene was analysed from 169 carcinoma specimens obtained from untreated patients with non-inflammatory breast cancer (NBC) (112 patients) and inflammatory breast cancer (IBC) (57 patients). A 3.5 kb c-myb transcript band was detected in 108 (64%) tumours. c-myb expression was found to be associated with good prognostic factors (lowest histopathologic grade (P = 0.01), oestrogen and progesterone receptor status (P less than 10(-4)) and pS2 gene expression (P less than 10(-4)) and negatively correlated with breast cancers of poorer prognosis, namely IBC (P = 0.03) and NBC with multiple involved nodes (P = 0.15). Other genes (c-myc, c-erbB2, c-fos and epidermal growth factor receptor) were also studied. The c-myb gene expression was found to be inversely correlated (P less than 0.03) with only c-erbB2 overexpression in NBC. When data were analysed with a logistic regression model using a stepwise procedure, c-myb expression was found to be associated only with the oestrogen receptor status (P less than 10(-4)). In conclusion, our data indicate that analysis of c-myb expression in breast cancer could allow the characterization of a new class of oestrogen-dependent tumours.
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PMID:Strong association between c-myb and oestrogen-receptor expression in human breast cancer. 218 74

Approximately 50% of human breast tumors secrete a small cysteine-rich protein called pS2. In the human breast cancer cell line MCF-7, expression of the pS2 protein is strongly induced by estrogen, and cloning and sequence analysis of the pS2 gene has revealed an "estrogen responsive element" in the gene's 5'-flanking region. The results of immunohistochemical assays and radioimmunoassays on breast cancer biopsies indicate that the pS2 protein is a marker for hormone-dependent breast tumors and that its expression is associated with longer overall, and disease-free, survival. The pS2 protein is also expressed in normal stomach mucosa and in regenerative tissues in ulcerative diseases of the gastrointestinal tract. Its physiological function is unknown.
Cancer Cells
PMID:The pS2 gene, mRNA, and protein: a potential marker for human breast cancer. 222 88

Estrogen-inducible pS2 mRNA was previously detected in human cancer cell lines the growth of which was sensitive to estrogen. In the present study, the expression of the pS2 gene was analyzed in 111 gynecological carcinomas. The pS2 message was detected in greatest abundance in 6 primary carcinomas of the ovary (6 of 29), 4 of these being mucinous cystadenocarcinomas. A secondary carcinoma of the ovary, and another of the omentum (1 of 4), also contained detectable levels of pS2 mRNA. Weak pS2 mRNA signals were occasionally observed in endometrial (2 of 55) and cervical carcinomas (2 of 33) as well. There was a poor correlation between estrogen receptor and pS2 mRNA in ovarian carcinomas.
Cancer Res 1990 Mar 15
PMID:Detection of pS2 messenger RNA in gynecological cancers. 230 33

Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2+) and negative (pS2-). Patients with pS2- tumors showed significantly shorter RFS and OS (P less than 0.0001) than patients with pS2+ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER+ tumors (53 of 55, 96%). The death rate for patients with pS2+ tumors was one-tenth of the death rate for patients with pS2-/ER- tumors. In the patients with ER+ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER+/PgR+/pS2+ tumors compared with 50% and 54% for the patients with ER+/PgR+/pS2- tumors). In patients with axillary lymph node involvement (N+), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N+/pS2+ compared with 32% and 34% for N+/pS2-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N0/pS2+ compared with 58% and 82% for N0/pS2-). We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER+/PgR+ subclass of tumors, and in both the N0 and N+ subclasses of patients.
Cancer Res 1990 Jul 01
PMID:Prediction of relapse and survival in breast cancer patients by pS2 protein status. 235 35

Xenograft tumours from an oestrogen-dependent human breast cancer cell line MCF-7 have been established and characterised in thymectomised, irradiated female CBA strain mice. There was evidence for selection in xenografts of a subpopulation of MCF-7 cells with an altered pattern of gene expression as measured by mRNA levels compared with the original cells in vitro. Tumorigenicity increased significantly on repeated animal passage but oestrogen dependence was retained. Following injection of the mice with oestrogen, mitosis was induced in the tumour cells with associated increases in thymidine uptake and percentage of cells in S-phase. In accord with these changes, c-myc and p53 expression were increased and TGF-beta was suppressed. Thereafter the expression of the c-myc and p53 genes fell whilst that of the TGF-beta gene was induced as the oestrogenic-stimulus declined. The oestrogen-regulated mRNA pS2 showed a biphasic response to oestrogen and levels declined as the serum oestrogen fell to undetectable levels. This xenograft system demonstrates that changes in transcription of oncogenes, growth factor and oestrogen-regulated genes can be detected in vivo in response to oestrogen. It thus provides an in vivo model for studies of the biochemical and molecular basis for therapeutic manipulation of hormone-sensitive human breast cancer.
Br J Cancer 1990 Jul
PMID:Gene expression in oestrogen-dependent human breast cancer xenograft tumours. 239 Apr 87

When deprived of steroid in the long term, both estrogen-dependent (ZR-75-1) and estrogen-responsive (T-47-D) human breast cancer cells lose estrogen regulation of cell growth in a reproducible time course using both stock lines and recloned cells. The estrogen-stimulated growth rate was unaffected by such treatment, but there was an increase in the basal growth rate without steroid. For ZR-75-1 cells, the effects are clonal but occur at high frequency (1 in 1000 cells) and synchronously between clones, suggesting a phenotypic mechanism. These changes in cell growth occur without any coordinated loss of estrogen sensitivity of molecular markers (pS2 mRNA, progesterone receptor protein) showing that functional estrogen receptors remain present throughout. The constitutive expression of progesterone receptor in one clone of steroid-deprived ZR-75-1 cells does suggest, however, that alterations in expression of individual estrogen-sensitive genes can occur. Loss of estrogen-stimulated growth was not accompanied by loss of growth inhibition by antiestrogen, and the latter effect remained reversible by estradiol. In an attempt to understand the molecular mechanisms underlying the loss of steroid sensitivity in the two cell lines, growth factor gene expression was investigated. Progression to steroid autonomy in T-47-D cells was accompanied by an upregulation of transforming growth factor (TGF) alpha, TGF beta 1, and TGF beta 2 mRNA. However, TGF beta 1 mRNA was downregulated in two ZR-75-1 steroid-deprived clones. These findings are discussed in relation to possible autocrine mechanisms in the loss of steroid sensitivity of breast cancer cells.
Cancer Res 1990 Sep 15
PMID:Cellular and molecular events in loss of estrogen sensitivity in ZR-75-1 and T-47-D human breast cancer cells. 239 57

A complementary DNA library was constructed from RNA of estrogen-stimulated MCF-7 cells and screened for estrogen-regulated sequences. Four different messenger RNA sequences of varying abundance were isolated. Two of the sequences (pNR-3 and pNR-4) were induced approximately 2-fold, while the other two (pNR-1 and pNR-2) were induced at least 8-fold. The induction of both pNR-1 and pNR-2 requires similar physiological concentrations of estradiol and is near maximal at 10(-10) M. An increase in the levels of the RNAs is seen after 30 min of estrogen treatment, but pNR-1 reaches its maximal concentration faster than pNR-2. pNR-1 and pNR-2 were not expressed in all human breast cancer cell lines tested. pNR-1 was expressed and regulated by estrogen in the estrogen receptor-positive cell lines, MCF-7, T-47D, and ZR 75, whereas pNR-2 was not expressed in the T-47D cell line. pNR-1 and pNR-2 were not detected in two estrogen receptor-negative cell lines (BT20 and HBL 100). As the proliferation of the MCF-7, T47D, and ZR 75 cell lines is stimulated by estradiol, pNR-1 may provide a useful marker of hormone-responsive breast cancer.
Cancer Res 1986 Dec
PMID:Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells. 243 Jun 88

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.
Int J Cancer 1989 Nov 15
PMID:Expression of the pS2 gene in normal, benign and neoplastic human stomach. 258 60

We have recently identified human epidermal growth factor-like immunoreactive factor synthesized and secreted by human breast cancer cells (MCF-7) as a secretory protein encoded by the pS2 gene, the transcription of which is directly induced by estrogen. We demonstrated in this paper that synthesis and secretion of pS2 protein as well as pS2 mRNA were induced about 5-fold specifically by physiological concentrations of estrogen, which stimulated growth of the cells about 5-fold. Stimulative effects of estrogen on both cell growth and synthesis/secretion of pS2 protein were inhibited completely by actinomycin D, cycloheximide, and antiestrogen. However, the increase in DNA synthesis from 6 h after the start of treatment of the cells with estrogen preceded the increase in the amount of pS2 protein in the culture medium from 12 h after that. Furthermore purified pS2 protein did not stimulate DNA synthesis of the cells. These results suggest that induction of pS2 protein by estrogen is not involved in the growth-stimulating effect of estrogen in MCF-7 cells.
Cancer Res 1989 Jul 01
PMID:Hormonal regulation of synthesis and secretion of pS2 protein relevant to growth of human breast cancer cells (MCF-7). 273 Nov 70


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