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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hamster ductus deferens cloned tumor cell line (DDT1) has been shown to contain both androgen and glucocorticoid binding activity. The androgen receptor binding site concentration is 1.07 x 10(-13) mol of testosterone/mg protein, and testosterone (T) binds with a Kd of 4.3 x 10(-10) M. Dihydrotestosterone (DHT) is also bound to the receptor with a Kd of 2.99 x 10(-10) M and the binding site concentration is 1.33 x 10(-13) mol/mg protein. The order of steroid binding affinity is DHT greater than T greater than Estradiol greater than Progesterone. Cortisol, dexamethasone, and triamcinolone acetonide do not inhibit the androgen binding in vivo or in vitro. In a cell free system antiandrogens inhibit the binding of DHT. The DDT1 cells have a separate receptor for cortisol which binds at saturation 3.44 x 10(-13) mol cortisol/mg protein and has a Kd of 4.54 x 10(-9) M. These studies provide evidence that these endocrine target cells contain specific high affinity receptors for more than one type of steroid. The glucocorticoid receptor may be important for maintaining essential undifferentiated functions while the DHT receptor gives the specific characteristics of sex hormone responsive tissues.
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PMID:The coexistence of androgen and glucocorticoid receptors in the DDT1 cloned cell line. 40 58

This study describes the distribution and frequency of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and glucocorticoid receptor (GR) in a large series of patients with primary metastatic breast cancer. 329 patients were in this series. All 4 steroid hormone receptors were present in the population: ER was positive in 53%, PR was positive in 38%, AR was positive for 31%, and GR was positive in 52%. Next, the distribution of ERs as well as the distributions of PR, AR, and GR values seemed unimodal. There was a very high correlation between any steroid hormone receptor value expressed as either fmol/mg of cytoplasmic protein or fmol/mg of breast tumor. Of more importance was that alternate methods of data expression did not alter the classification of values as positive or negative. No correlation was found between any of the steroid hormone receptors and laterality of the breast tumor, location and size of the primary tumor, extent of disease, or type of tissue assayed. None of the steroid hormone receptors correlated with age. There was a strong correlation noted between ER values and menopausal status. Neither PR, AR, nor GR was significantly associated with menopausal status. ER status was correlated with axillary nodal status, with the ER positive group containing a high proportion of node-negative patients. Finally, quantitative analysis of steroid receptor hormone values demonstrated correlations among other receptors. Plotting values of any 1 receptor vs. any other receptor resulted in a positive Kendall rank test correlation which was highly significant.
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PMID:Distribution, frequency, and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer. 42 88

85 patients with metastatic or surgically unrecsectable primary breast cancer who had had 1 or more steroid hormone receptor assays performed immediately before the institution of endocrine therapy were studied retrospectively to determine any influence of steroid hormone receptors on response rate to endocrine therapy. Included in addition to effects of estrogen receptor (ER) status are the effects of androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) on therapy perfornamce. Of 18 patients whose tumor contained PR, 11 responded to endocrine therapy, compared with 8 of 26 patients with low or absent PR. PR increased the predictive index of the ER in an group of patients who had received no prior therapy, but it did not help in patients who had received prior endocrine therapy. 0 of 4 patients whose tumors were ER negative but PR positive responded to endocrine therapy. Present trends suggest a possible association between AR and GR and response to endocrine therapy. A cut-off value of 10 fmol/mg of cytoplasmic protein was needed to make these trends apparent. The distributions of AR and GR values for responders and nonresponders were not significantly different. Knowledge of AR status does not increase the protective index in ER-positive or ER-negative tumors. GR positivity may increase the predictive index in ER-positive tumors, but not in ER-negative ones.
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PMID:Relationship between the progesterone, androgen, and glucocorticoid receptor and response rate to endocrine therapy in metastatic breast cancer. 44 96

The size of androgen receptors from rat ventral and dorsal prostate, dorsal prostate (Dunning) tumor, testis, epididymis, and seminal vesicle was determined using Sephadex G-200 chromatogrpahy and sucrose gradient centrifugation. The protease inhibitor diisopropyl fluorophosphate (DFP) was used to minimize receptor breakdown. An 8-9 S, 85 to 106 A receptor (Mr = 280,000 to 365,000; f/fo = 1.9 to 2.4) observed in unfractionated cytosol prepared in low ionic strength buffer with or without DFP is in equilibrium with a 4.5-5 S, 58 A form (Mr = 117,000; f/fo = 1.8) observed at salt concentrations greater than 0.1 M KCl. Receptor partially purified using (NH4)2SO4 or phosphocellulose chromatography in the absence of DFP was present as smaller fragments of 3.6 S, 37 A and 3.0 S, 23 A. Similar fragments could be generated from the 4.5 S or 8 S receptor by mild trypsin treatment. In addition, ventral prostate contains a DFP-insensitive enzyme which specifically converts the 4.5 S, 58 A receptor to the 3.6 S 37 A fragment. The DFP-insensitive enzyme is partially inhibited by rabbit bile and appears similar to the enzyme seminin, a secretory protein of human prostate. Androgen receptor isolated in the presence of DFP from nuclei labeled in vivo is predominantly 4.5 S, 58 A, with smaller forms (37 and 23 A) appearing in the absence of DFP. The 4.5 S, 58 A nuclear receptors were also in equilibrium with a large 8 S form. Receptor breakdown by DFP-insensitive and sensitive proteases appears to be an in vitro phenomenon. Furthermore, the size of the androgen receptor is not significantly changed during receptor migration from cytoplasm to nucleus.
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PMID:Effects of proteases and protease inhibitors on the 4.5 S and 8 S androgen receptor. 44 15

When Shionogi carcinoma 115 (SC115, undifferentiated medullary carcinoma showing compact cell pattern and containing androgen receptor) was transplanted into male and female DS mice, it grew only in males. In contrast to this strict androgen dependency in DS hosts, tumors composed of spindle-shaped cells appeared in more than 80% of cases when SC115 tumor was inoculated into female or castrated male nude athymic (BALB/c-nu/nu) recipients. These spindle cell tumors neither contained cytosol androgen receptor nor showed biologically defined androgen dependency. As spindle cell tumors could be serially transplanted in DS mice but not in BALB/c-+/+ mice and as the original SC115 (medullary carcinoma showing a compact cell pattern) tumor and the spindle cell tumor had many identical chromosome abnormalities, these two types of tumors seem to have a common origin in spite of their morphological, biochemical, and biological differences. Since spindle cells could not be detected histologically in SC115 tumors maintained in intact male DS mice, the present results seem to suggest that SC115 cells may change their morphological, biochemical, and biological characteristics within one passage in androgen-depleted nude athymic mice.
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PMID:Development of androgen-independent spindle cell tumors from androgen-dependent medullary Shionogi carcinoma 115 in androgen-depleted nude mice. 49 97

A comprehensive study of the R-3327 line of prostate adenocarcinoma of the Copenhagen rat was performed. This tumor, investigated in its histologic, endocrinologic, and immunologic aspects, was compared with a squamous cell prostate carcinoma derived from the R-3327. The two tumor lines differ in their rates of growth and in their androgen receptor contents, i.e., the adenocarcinoma is androgen dependent and grows slowly, whereas the squamous cell carcinoma has a rapid rate of growth and is androgen independent. A study of cell-mediated immune responses revealed that: 1) Nonspecific responses to mitogens in the blastogenic assay, as well as antibody-dependent cellular cytotoxicity, are enhanced in animals bearing tumors. 2) The R-3327 is immunogenic to its host as demonstrated by two parameters. 3) The antigens present in the squamous cell carcinoma are not recognized by lymphocytes of the animals bearing the adenocarcinoma, substantiating the specificity of the reaction. For these reasons, the system of R-3327 prostate adenocarcinoma provides a relevant model for the study of prostate cancer.
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PMID:Characterization of prostate carcinoma lines in the Copenhagen rat. 74 80

Several histologic variants of the transplantable R-3327 prostatic adenocarcinoma carried in male Copenhagen rats have been characterized and the histologic types have been correlated with steroid hormone receptor content. One type is clearly an adenocarcinoma; this tumor is hormonally responsive and contains substantial amounts of both androgen and estrogen receptors. In contrast, another histologic type, a fibrosarcoma, is hormonally nonresponsive and does not contain either receptor. A third histologic variant is classified as a carcinosarcoma and contains histological elements of both adenocarcinoma and fibrosarcoma and is also hormonally responsive. This tumor contains lower receptor levels than the adenocarcinomas but more than the fibrosarcomas. The androgen receptor appears to be identical in the different histologic forms of the tumor: the sedimentation coefficient is 7.8S and the dissociatiln constant for methyltrienolone is 4 x 10(-9) M. Similarly, the estrogen receptor from the different histologic forms of the tumor has a sedimentation coefficient of 8.3S and the dissociation constant for estradiol is 7 x 10(-10) M. These findings clearly distinguish the cytosol binding macromolecules from plasma binding proteins, and classify them as steroid hormone receptors. Further, rat serum was devoid of androgen and estrogen binding in the 8S region. Normal prostate tissue from Copenhagen rats contained low levels of an androgen receptor, but no estrogen receptor. It is possible that during growth and/or passage of the R-3327 tumor, the hormonally responsive adenocarcinoma cells do not survive and there is a gradual emergence of the nonresponsive fibrosarcoma. If, as we suspect, the receptors are found in the epithelial cells and not the stromal cells, there clearly should be considerable variation of receptor content in the different intermediary histologic forms of the tumor.
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PMID:Steroid hormone receptor characterization of several histologic variants of a rat prostatic adenocarcinoma. 75 Jul 63

To facilitate an understanding of how androgens participate in the genesis of human benign hyperplasia and carcinoma we assayed androgen receptor in the epithelium and stroma of human prostatic tissue from 57 patients. Immunohistochemical staining of human androgen receptor was performed on 106 sections of normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. To determine variability of androgen receptor staining sections taken from different portions of the gland were studied. Frozen tissue sections were incubated with monoclonal antiandrogen receptor antibodies and staining was completed by the indirect avidin-biotin peroxidase method. Antibody staining was found mainly in the nucleus of prostatic epithelial cells, although some stromal cells also showed positive staining. Unlike normal prostate, there was a heterogeneous distribution of androgen receptor in BPH and prostate cancer. The androgen receptor content in well differentiated adenocarcinoma epithelium was significantly higher compared to moderately (p less than 0.05) and poorly (p less than 0.05) differentiated adenocarcinoma. Regardless of the origin of stromal tissue, some staining was observed. In each specimen studied the androgen receptor staining was consistent qualitatively and quantitatively for each pathological component throughout the specimen. These data confirm that androgen receptor is a nuclear receptor protein. Furthermore, they show the ability of monoclonal antibodies to reveal cellular/subcellular distribution of androgen receptor, and demonstrate a correlation between the degree of tumor differentiation and androgen receptor content in epithelial but not in stromal cells. These observations may have important implications for understanding the variable tumor response to hormone therapy.
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PMID:Nuclear localization of androgen receptor in heterogeneous samples of normal, hyperplastic and neoplastic human prostate. 137 52

Prostate-specific antigen (PSA) is the most sensitive marker available for monitoring the progression of prostate cancer and response to therapy. In a previous study, we demonstrated tissue-specific expression of PSA glycoprotein and mRNA and its regulation through the androgen receptor. In this study, we examine the effects of protein kinase A (PKA) and protein kinase C (PKC) on the androgen regulation of PSA in a human adenocarcinoma cell line, LNCaP. Northern blot analysis demonstrated that forskolin, an activator of PKA, had no effect on the androgen regulation of PSA. However, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a direct activator of PKC, showed a time- and dose-dependent repression of the androgen regulation of PSA glycoprotein and mRNA. The biologically inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, had no effect. Staurosporine, a PKC inhibitor, blocked the TPA-mediated repression of the androgenic stimulation of PSA glycoprotein. In addition, the calcium ionophore, A23187, was able to simulate the actions of TPA, presumably through activation of PKC via calcium mobilization. In summary, the androgenic regulation of PSA protein and mRNA is repressed by tumor-promoting phorbol esters through the PKC pathway. This indicates that the effects of TPA may be secondary to repressed gene transcription or altered mRNA stability. In addition, this study emphasizes that the androgenic regulation of PSA is complex and may involve other extracellular transduction signals.
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PMID:Tumor-promoting phorbol ester down-regulates the androgen induction of prostate-specific antigen in a human prostatic adenocarcinoma cell line. 137 17

In vivo effects of androgen withdrawal and substitution on human androgen receptor (hAR) expression were evaluated in the androgen-dependent human prostatic carcinoma tumor line PC-82. By application of several antibodies reactive with different epitopes of the hAR molecule, hAR protein expression was studied in tumor transplants by immunohistochemistry and immunoblotting. hAR messenger RNA (mRNA) levels were quantitated in PC-82 tumor tissue with a S1-nuclease protection assay. Most PC-82 tumor cells (> 97%) from testosterone-supplemented mice displayed nuclear hAR protein expression immunohistochemically. The almost complete reduction of nuclear hAR immunoreactivity within 5 days after androgen withdrawal (< 10%) was restored after androgen substitution within 1 day. The immunochemical data were confirmed by Western blot analysis. In contrast, no significant changes were observed in hAR mRNA content of PC-82 cells after 5 days of androgen withdrawal. Correlating hAR expression with proliferative activity of PC-82 tumor tissue during endocrine manipulation, a rapid, castration-induced decline of the percentage of bromodeoxyuridine-labeled cells accompanied the loss of hAR. Androgen substitution in castrated male mice restored the proliferative activity. However, this increase of proliferative activity lagged at least 24 h behind the normalization of the hAR protein level. In contrast to the steroid receptor down-regulation by homologous ligands observed in other experimental models, our data support the concept of hAR up-regulation by androgen. Since the hAR mRNA content of PC-82 tumor tissue was hardly affected by castration, expression of the hAR in PC-82 is thought to be modulated by translational and/or posttranslational mechanisms.
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PMID:Regulation of androgen receptor expression in the human heterotransplantable prostate carcinoma PC-82. 144 39


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