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)

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.
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PMID:Detection of pS2 messenger RNA in gynecological cancers. 230 33

NH2-terminal amino acid sequence of the pS2 protein produced and secreted by human gastric cancer cells, MKN-45, was determined to be identical to that of MCF-7 cells. A clone encoding pS2 protein was isolated from the cDNA library constructed from MKN-45 cells. The nucleotide sequence was identical to that of pS2 cDNA previously isolated from human breast cancer cells, MCF-7, except for one nucleotide in the 3' untranslated region. Thus, in this cell line, the pS2 gene product is translated and secreted as in MCF-7 cells. RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation. These results suggest that pS2 is expressed in human gastric cancer cells in an estrogen-independent manner and is possibly associated with the malignant state of cells.
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PMID:Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma. 231 59

The expression of genes specifically induced by estrogens (pS2), prolactin (PIP) or progestins (Pg8) was measured in primary breast tumours. A highly augmented pS2 gene expression was evident in 55% of estrogen receptor (ER)+, progesterone receptor (PR)+ tumours but was absent in ER- PR- tumours. There was no clear cut correlation between augmented levels of PIP and Pg8 mRNAs in tumours and ER and PR status. Tumours from premenopausal patients were more likely to contain high levels of Pg8 mRNA (P less than 0.038), whereas tumours from postmenopausal patients tended to have augmented levels of PIP mRNA (P less than 0.053).
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PMID:Hormone-sensitive gene expression in breast tumours. 233 25

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.
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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.
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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.
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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.
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PMID:Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells. 243 Jun 88

The pS2 gene is transcriptionally induced by oestrogen in the human breast cancer cell line MCF-7. We demonstrate here that the 5' flanking sequences (-3000 to +10 bp) of the pS2 gene possess the properties of an oestrogen-inducible promoter. Interestingly, this oestrogen induction could not be demonstrated in transient transfection assays in MCF-7 cells, but only in stably transformed MCF-7 cells, which suggests that some factors responsible for oestrogen induction may be present in limiting amounts in these cells and absent in HeLa cells.
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PMID:The 5' flanking region of the human pS2 gene mediates its transcriptional activation by estrogen in MCF-7 cells. 245 May 36

Two cDNA libraries have been constructed with RNA prepared from the estrogen-responsive breast cancer cell lines, MCF7 and ZR 75. They were screened by differential hybridization for estrogen-regulated sequences. A total of 11 different RNAs were isolated from the MCF7 cell cDNA library and four from the ZR 75 cell cDNA library. Only two sequences were isolated from both libraries. The levels of the 13 different RNAs are induced between 2.5- and 100-fold by estrogen in MCF7 cells. The expression and regulation by estrogen of the RNAs was examined in eight different human tumor cell lines. The relative abundance of each RNA varied in the different cell lines. The expression of three RNAs (pNR-1, pNR-2, and pNR-25) was detected only in estrogen-responsive breast cancer cells. The sequences that were expressed in all eight cell lines were regulated by estrogen only in the three estrogen-responsive breast cancer cell lines. The response of the RNAs to other classes of steroids and to different concentrations of estrogen was characterized in more detail. The extent to which different concentrations of estradiol induced each RNA varied, but half-maximal induction of most of the RNAs occurred between 2 and 5 X 10(-11) M. The time at which increased RNA levels were first detected following exposure to estradiol also varied. Estrogen increased the levels of some RNAs within 15 min, while for others there was a lag of 4 h.
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PMID:Identification and characterization of estrogen-regulated RNAs in human breast cancer cells. 245 37

We have examined the effects of reversibly and irreversibly binding estrogenic and antiestrogenic ligands for the estrogen receptor on pS2 RNA accumulation in MCF-7 human breast cancer cells and on pS2-chloramphenicol acetyl transferase (CAT) fusion gene expression in transfected MCF-7 cells. In MCF-7 cells grown in the absence of estrogens, the reversibly binding estrogen, estradiol, and the affinity labeling estrogen, ketononestrol aziridine, KNA, evoked a 13-fold increase in pS2 RNA level. The reversibly binding antiestrogen trans-hydroxytamoxifen and the affinity labeling antiestrogens tamoxifen aziridine or desmethylnafoxidine aziridine behaved as partial agonists/antagonists. In thymidine kinase-chloramphenicol acetyltransferase (tk-CAT) fusion genes containing a 1000 base pair fragment of the pS2 5'-flanking region encompassing the estrogen responsive element of the gene [pS2 (-1100/-90) tk-CAT], estradiol and ketononestrol aziridine evoked a marked stimulation of CAT activity and, in transfected cells grown in both the presence or absence of the weak estrogen phenol red, the antiestrogens behaved as partial agonists/antagonists. This pS2 5'-flanking region displayed both estrogen-dependent and estrogen-independent enhancer activity as monitored by stimulation of CAT activity. Hormonal regulation of the transfected pS2 fusion gene was similar to that observed in the native pS2 gene of MCF-7 cells; however, antiestrogens, while still partial agonists-antagonists, were relatively more agonistic on the transfected fusion gene than on the native gene. One antiestrogen (ICI 164,384) that behaved as a pure estrogen antagonist on the native gene was a partial agonist-antagonist of pS2 gene expression in the plasmid. This study illustrates that the hormonal regulation of the pS2 gene, as characterized by the agonist-antagonist balance of estrogens and antiestrogens, is influenced by the DNA context of the pS2 estrogen responsive element. Also, the fact that estrogens and antiestrogens that form covalent bonds with the estrogen receptor modulate activity of the native pS2 gene and the pS2-tk-CAT fusion gene in a manner similar to that of their reversibly binding counterparts suggests that it may be possible to use these irreversibly binding ligands to follow the interaction of hormone-receptor complexes with regions regulating estrogenic stimulation of the pS2 gene.
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PMID:Regulation of pS2 gene expression by affinity labeling and reversibly binding estrogens and antiestrogens: comparison of effects on the native gene and on pS2-chloramphenicol acetyltransferase fusion genes transfected into MCF-7 human breast cancer cells. 246 Jul 49


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