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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cathepsin D gene is differentially regulated by estrogens in hormone responsive breast cancer cells, by progestins in normal human endometrium and is highly expressed but not regulated by these steroids in estrogen (RE)- and progesterone receptor (RP)-negative breast cancer cells. We have stably transfected the RE-negative breast cancer cell line MDA-MB 231 and the Hela cell line with an expression vector for the human RE. The endogenous cathepsin D which is constitutively expressed was further stimulated by estradiol. However, the growth of both cell lines was not stimulated by estradiol and could not be inhibited by the antiestrogen ICI 164,384. By contrast, the cathepsin D gene in the estrogen responsive Ishikawa endometrial cancer cell line was unresponsive to estrogen or to progesterone even following stable transfection of expression vectors for the RP (both A and B isoforms). We conclude that the cathepsin D gene is potentially responsive to estrogens in MDA-MB 231 and Hela cells, which therefore express all of the transcriptional machinery (except the RE) necessary for this regulation. By contrast, cathepsin D remains unresponsive to estrogen and progesterone in Ishikawa cells. The cathepsin D gene is one of the first examples of an endogenous steroid responsive gene which can be controlled by steroids following stable transfection of a steroid receptor.
J Steroid Biochem Mol Biol 1991
PMID:Hormonal regulation of cathepsin D following transfection of the estrogen or progesterone receptor into three sex steroid hormone resistant cancer cell lines. 195 26

The progesterone receptor belongs to a class of ligand binding transcription factors that regulate transcription by interacting with specific DNA sequences on hormone regulated genes. In human mammary tumor T47D cells that contain both progesterone and epidermal growth factor (EGF) receptors, the progestin-induced transactivation at various hormone regulated promoters is enhanced by EGF. The effect of EGF is rapid and does not require new protein synthesis. EGF treatment does not alter the DNA binding activity of the progesterone receptor nor does it affect the total ligand-dependent phosphorylation of this receptor. These results suggest that EGF enhances the transactivation property of the progesterone receptor through mechanisms other than those involving a direct interaction of this receptor with its cognate binding sites.
J Steroid Biochem Mol Biol 1991
PMID:Co-operation of progestational steroids with epidermal growth factor in activation of gene expression in mammary tumor cells. 195 27

We present evidence that the two isoforms of A and B of the chicken (cPR) and human progesterone receptor (hPR) originate from two different mRNA populations. One of these encodes the isoforms A which originate by initiation of translation at an in-frame AUG found 127 (cPR) and 165 (hPR) codons downstream of the AUG which gives rise to the isoforms B. Two estrogen-inducible hPR promoters were identified which are responsible for the generation of these two classes of transcripts. Characterization of the cPR promoter suggested the possible existence of cell-type and isoform-specific auto-regulation of cPR transcription and provided evidence that estrogen-induction of cPR expression occurs at a post-transcriptional level. Finally, we demonstrate promoter-specific transcriptional activation by the hPR isoforms A and B, and we discuss the mechanism of action of the anti-progestin RU486.
J Steroid Biochem Mol Biol 1991
PMID:Progestin receptors: isoforms and antihormone action. 195 31

A clear neuroendocrine sex difference lies in the ability of the female rat to produce an ovulatory surge of luteinizing hormone. Preoptic neurons, as they respond to estrogen and progesterone, have been proven to be involved in this mechanism, with an emphasis on the possible participation of neurons in the anteroventral periventricular nucleus and the suprachiasmatic portion of the preoptic area (POA). Further, prominent morphological sex differences have been reported in the rat medial POA. To examine expression of the estrogen receptor (ER) and the progesterone receptor (PR) messenger RNAs (mRNAs) in these critical preoptic neurons, we have used in situ hybridization with tritiated single-stranded DNA probes complimentary for ER and PR mRNA. ER mRNA containing cells were found in the periventricular, suprachiasmatic and medical preoptic cell groups, in a manner which agrees with steroid hormone autoradiography. In the female rat, preoptic neurons expressing PR mRNA were distributed very similarly to those for ER mRNA. Moreover, in the male rat brain, all subsets of preoptic neurons which express the PR gene in the female were also detected in the male. Thus, the distribution of PR expressing cells was very similar between females and males. We conclude that the insensitivity to the male to progesterone, as regards the hormonal control of ovulation, cannot be due to a total failure of PR gene expression in a specific subset of POA neurons. Instead, male preoptic neurons must be less sensitive to neural or hormonal inducers in the physiological range or perhaps lack sufficient levels of a transcription factor linking progesterone responsive elements to the start sites of hormone-controlled genes.
J Steroid Biochem Mol Biol 1991
PMID:Gene expression for estrogen and progesterone receptor mRNAs in rat brain and possible relations to sexually dimorphic functions. 195 49

An increasing body of evidence suggests that breast tumour growth is mediated by oncogene products and growth factors which are or which act through cell surface receptors. The aims of the present study were to determine how three of these receptors, c-erbB-2 protein, epidermal growth factor receptor (EGFr) and the beta-subunit of platelet-derived growth factor receptor (PDGFr-beta-subunit), can effectively be demonstrated by immunohistochemical methods in breast tumors, how these receptors are distributed at the cellular level and how their expression correlates with well-established prognostic indicators including hormone receptors and proliferative index. We examined frozen tissue sections of 50 invasive human breast carcinomas, including 45 ductal, four lobular, and one mucinous tumours, by immunocytochemical methods to determine the in situ distributions of c-erbB-2, EGFr, and PDGFr-beta-subunit. We compared staining for c-erbB-2 protein in frozen sections with that in paraffin sections of the same 50 tumours. The immunohistochemical labelling results were compared with tissue hormone receptor content and growth fraction determined by Ki-67 labelling. Strong labelling of tumour cells in frozen sections was detected in 22% of cases, all of the ductal type, stained with rabbit antiserum to c-erbB-2. Labelling for c-erbB-2 protein was generally weaker in paraffin sections than in frozen sections and in six of 11 positive cases, specific staining could be detected only in frozen sections. In immunostains with monoclonal antibody to EGFr, rare cells within tumour were labelled in 60% of the carcinomas. Using a monoclonal antibody to the beta-subunit of PDGFr, consistent labelling of fibrillary cellular processes in the walls of blood vessels and in fibrous stroma around tumour cell nests was detected, but there was no labelling of tumour cells themselves. C-erbB-2 oncoprotein positive tumours were found to be more often oestrogen receptor negative (P less than 0.005) or oestrogen and progesterone receptor negative (P less than 0.01) than c-erbB-2 negative tumours. No significant correlation was observed between c-erbB-2 expression and Ki-67 growth fraction.
Mol Cell Probes 1990 Feb
PMID:In situ distribution of oncogene products and growth factor receptors in breast carcinoma: c-erbB-2 oncoprotein, EGFr, and PDGFr-beta-subunit. 196 11

In order to determine if different physicochemical properties exist among antihormone-receptor complexes, we have compared the interaction of the antiprogestin RU486 with progesterone receptor (PR) versus the triphenylethylene antiestrogen H1285 (4-(N,N-diethyl-aminoethoxy)-4'-methoxy-alpha-(p-hydroxyphenyl-alp ha'- ethylstilbene] with estrogen receptor (ER) from rabbit uterine tissue. Contrary to other reports, we observed no difference in the sedimentation properties of transformed PR (4S) when bound by the antagonist RU486 versus the progesterone agonist R5020 in either cytosol or DEAE partially-purified receptor preparations analyzed on sucrose gradients containing 0.3 M KCl. In addition, we found no difference in the sedimentation properties of these receptor preparations in the presence of 10 mM sodium molybdate: the nontransformed RU486-PR and nontransformed R5020-PR both sedimented as a 6S species. These same results were obtained when the receptor preparation and gradient analysis were performed in the absence of monothioglycerol. Likewise, there was no change in the sedimentation properties of the transformed PR when the receptor, partially purified in the absence of molybdate, was analyzed on sucrose gradients containing 10 mM sodium molybdate to prevent receptor alteration during centrifugation. From DNA-cellulose assays performed with partially purified PR in the absence of molybdate we determined that the 4S form of R5020-PR and RU486-PR is transformed receptor; whereas in the presence of molybdate, the 6S species is nontransformed. In contrast, we found a different pattern of sedimentation when comparing transformed antiestrogen-receptor complexes with transformed estrogen-receptor complexes. In this case, transformed H1285-ER sedimented as 6S and estradiol-ER sedimented as 4S. We conclude from these experiments that these two antihormones, RU486 and H1285, may have different mechanisms of action in their antagonism of steroid hormone action. Antiestrogen stabilizes the salt-transformed ER as a dimer while antiprogestin appears to permit dissociation of the oligomeric form of the receptor to the monomeric form.
J Steroid Biochem Mol Biol 1991 Feb
PMID:Effects of antiestrogen versus antiprogestin on transformed and nontransformed steroid receptors. 200 41

Steroid hormone receptors can be divided into two subfamilies according to the structure of their DNA binding domains and the nucleotide sequences which they recognize. The glucocorticoid receptor and the progesterone receptor (PR) recognize an imperfect palindrome (glucocorticoid responsive element/progesterone responsive element [GRE/PRE]) with the conserved half-sequence TGTYCY, whereas the estrogen receptor (ER) recognizes a palindrome (estrogen responsive element) with the half-sequence TGACC. A series of symmetric and asymmetric variants of these hormone responsive elements (HREs) have been tested for receptor binding and for the ability to mediate induction in vivo. High-resolution analysis demonstrates that the overall number and distribution of contacts with the N-7 position of guanines and with the phosphate backbone of various HREs are quite similar for PR and ER. However, PR and glucocorticoid receptor, but not ER, are able to contact the 5'-methyl group of thymines found in position 3 of HREs, as shown by potassium permanganate interference. The ER mutant HE84, which contains a single amino acid exchange, Glu-203 to Gly, in the knuckle of ER, creates a promiscuous ER that is able to bind to GRE/PREs by contacting this thymine. Elements with the sequence GGTCAcagTGTYCT that represent hybrids between an estrogen response element and a GRE/PRE respond to estrogens, glucocorticoids, and progestins in vivo and bind all three wild-type receptors in vitro. These hybrid HREs could serve to confer promiscuous gene regulation.
Mol Cell Biol 1991 Jun
PMID:Functional interaction of hybrid response elements with wild-type and mutant steroid hormone receptors. 203 29

The T47-D breast cancer cell line constitutively expresses high levels of progesterone receptor (PR). This does not appear to be related to an anomaly in the estrogen receptor (ER) as shown by cloning of the ER cDNA from T47-D cells and its insertion into the expression vector pKSV-10. When transfected into heterologous Cos-7 and L cells this receptor exerts a normal biological activity, stimulating the transcription of a reporter gene only in the presence of estrogen. Moreover, normal estrogen regulation of the transcription of the reporter gene was also observed in situ in T47-D cells. Southern blot experiments showed the presence of four copies of the progesterone receptor gene in T47-D cells. This was related to the existence of four copies of chromosome 11 in these cells. The most likely explanation of the anomalous regulation of progesterone receptor expression in T47-D cells is thus the presence of at least one copy of the PR gene bearing an anomaly in its regulatory region(s).
Mol Cell Endocrinol 1991 Feb
PMID:Origin of the high constitutive level of progesterone receptor in T47-D breast cancer cells. 205 Feb 75

Progesterone enhances the synthesis of a 42 kDa protein secreted by rabbit endometrial stromal cells in primary culture. The duration of that response, the effects of estrogen and the inhibitory ability of antiprogestin steroid analogs, RU486, ZK98.299 and ZK98.734, were tested. Although there was a progressive decrease in the amount of the 42 kDa protein synthesized during a 6-day culture period, progesterone stimulated its rate of synthesis greater than 2-fold throughout that period. The addition of estrogen did not prevent the progressive decrease in the amount of the protein synthesized, nor did it enhance the progesterone effect when the culture medium contained phenol red. Estrogen alone did slightly induce 42 kDa protein synthesis by cells grown in phenol red-free medium, and the progesterone response was accentuated to the same degree. When present in a concentration that was 100-fold that of the progesterone, RU486, ZK98.299 and ZK98.734 each abolished stimulation. This antagonistic effect was overcome by addition of an equimolar concentration of progesterone. Deoxycorticosterone (DOC) also stimulated 42 kDa protein synthesis. The antiprogestins blocked this stimulatory effect, even when both steroids were in equimolar concentrations. There was no difference in the ability of ZK98.299 or ZK98.734 to block DOC stimulation, even though ZK98.734 exhibits no antiglucocorticoid activity [J. Steroid Biochem. 25 (1986) 835]. Therefore, it is likely that the DOC effect is mediated by the progesterone receptor system. These studies indicate that enhanced synthesis of the 42 kDa protein represents a progesterone receptor mediated event and that the cell culture system described can be used as a bioassay for determination of antiprogestin activity.
J Steroid Biochem Mol Biol 1991 Jul
PMID:Effects of progestin antagonists, glucocorticoids and estrogen on progesterone-induced protein secreted by rabbit endometrial stromal cells in culture. 206 62

We performed in situ hybridization on hypothalamic sections from ovariectomized guinea pig using a cocktail of three 35S-labeled oligonucleotides complementary to mammalian progesterone receptor (PR) cDNA. PR mRNA was readily detected in hypothalamic neurons from guinea pigs pretreated with 17 beta-estradiol benzoate (E2B), but not from animals which did not receive supplemental E2B. The distribution of PR mRNA-containing cells corresponded well with previous localizations of PR in guinea pig. In contrast to earlier reports of E2B regulation of PR mRNA in rat hypothalamus, however, we found that PR mRNA remained elevated during chronic exposure to E2B (up to 10 days) in guinea pig.
Brain Res Mol Brain Res 1991 May
PMID:Chronic estrogen exposure maintains elevated levels of progesterone receptor mRNA in guinea pig hypothalamus. 207 27


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