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

We compared six inbred mouse strains for their relative susceptibilities to liver and lung tumor induction. Male and female mice were treated at 12 days of age with a single i.p. injection of N-ethyl-N-nitrosourea (ENU; 0.25 mumol/g), and tumor multiplicity was analyzed at 32 weeks of age (males) or 44 weeks of age (females). Male mice of the SWR/J and C57BL/6J strains were relatively resistant to hepatocarcinogenesis, averaging 0 and 0.3 tumors per animal, respectively. Male C57BR/cdJ, P/J, and SM/J mice had intermediate susceptibilities, averaging seven to 17 tumors per animal, and male CBA/J mice were the most susceptible, averaging 45 tumors per animal. Female mice were more resistant than male mice: no liver tumors were observed for SWR/J females; C57BL/6J, SM/J, P/J, and CBA/J females averaged less than one tumor per animal and C57BR/cdJ females averaged five tumors per animal. In contrast to the results for liver tumor induction, there was no difference between the sexes in lung tumor susceptibility. Male and female SWR/J mice were the most susceptible, averaging 14 lung tumors per animal; male and female CBA/J mice were moderately susceptible, averaging six tumors per animal and the C57BR/cdJ, C57BL/6J, P/J, and SM/J strains were relatively resistant, averaging less than three tumors per animal. To determine if levels of testosterone, a potent liver tumor promoter in mice, or its receptor contribute to the strain variation in liver tumor susceptibility, we measured levels of plasma testosterone as well as binding properties of the hepatic androgen receptor for the six inbred strains. Plasma testosterone in male mice ranged from 1.8 to 7.4 ng/ml and in females ranged from 0.21 to 0.42 ng/ml, which is consistent with the greater susceptibility of male mice to liver tumor development. However, variation in testosterone levels among the different strains of mice was not correlated with liver tumor susceptibility. We also demonstrated the presence of high affinity androgen receptors in mouse hepatic cytosol. The amounts of this receptor for the six strains tested ranged from 24 to 34 fmol/mg cytosolic protein. The apparent KD of the receptor for [3H]mibolerone (a synthetic androgen) differed between the strains: SWR/J, C57BL/6J, and C57BR/cdJ mice had the highest affinity (KD = 0.22 nM), P/J and CBA/J strains had an intermediate affinity (KD = 0.36 nM), and the SM/J strain had the lowest affinity receptor (KD = 0.45 nM). The strain variation in the affinity or abundance of the androgen receptor was not related to the strain variation in liver tumor induction.
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PMID:Genetic variation in liver tumor susceptibility, plasma testosterone levels, and androgen receptor binding in six inbred strains of mice. 276 75

Tfm (testicular feminization) mutant mice lack functional androgen receptors. By studying liver tumor development in Tfm mice, we have shown that the greater susceptibility of male mice relative to female mice for liver tumor induction by N,N-diethylnitrosamine is androgen receptor-dependent. C57BL/6J normal and Tfm mutant mice were injected at 12 days of age with N,N-diethylnitrosamine (0.2 mumol/g, i.p.), and liver tumors were enumerated in 50-week-old animals. Normal males averaged 20 liver tumors per animal; Tfm males, 0.7; normal females, 0.6; and Tfm/+ heterozygous females, 1.5. The androgen receptor gene and the Tfm mutation are X chromosome linked. Because of random X chromosome inactivation, hepatocytes from Tfm/+ heterozygous female mice are mosaic with respect to the expression of mutant or wild-type receptors. To determine if testosterone acts directly as a liver tumor promoter, through the androgen receptor in preneoplastic hepatocytes, or by an indirect mechanism, we chronically treated these mosaic female mice with testosterone and measured the androgen receptor content of the resulting tumors. B6C3F1 Tfm/+ mosaic and +/+ wild-type female mice were injected i.p. at 12 days of age with N,N-diethylnitrosamine (0.1 mumol/g) and ovariectomized at 8 weeks of age. Half of the mice of each group subsequently received biweekly s.c. injections of testosterone (0.15 mg per mouse) for 30 weeks. Tumor multiplicity was the same for wild-type and Tfm/+ mosaic females treated with testosterone (31-32 tumors per animal at 38 weeks of age) and was increased relative to females not treated with testosterone (13-17 tumors per animal at 50 weeks of age). Testosterone treatment did not significantly increase the percentage of androgen receptor-positive tumors in Tfm/+ mosaic females: 58% of the tumors from Tfm/+ mosaic females treated with testosterone were receptor positive compared to 48% in Tfm/+ females not treated with testosterone and 92% in wild-type females treated with testosterone. Finally, the number of androgen receptors in the majority of liver tumors examined was greatly decreased relative to the surrounding normal liver tissue. We conclude that liver tumor promotion by testosterone requires a functional androgen receptor in the intact animal. However, this promotion is not cell autonomous; that is, the response of the preneoplastic hepatocyte is not dependent on the expression of functional receptor in the target cell.
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PMID:Promotion of murine hepatocarcinogenesis by testosterone is androgen receptor-dependent but not cell autonomous. 279 21

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.
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PMID:Androgen receptors in experimentally induced colon carcinogenesis. 294 49

Hormone sensitivity, as indicated by the presence of steroid hormone receptors and by the effect of androgens and anti-androgens on the release of proteins by cultured cells of the human prostate tumor cell line lymph node carcinoma of the prostate-fast growing colony (LNCaP-FGC), has been studied. The growth of the LNCaP-FGC cells were stimulated by androgens in a dose-dependent way. Under optimal conditions the synthetic nonmetabolizable androgen 17 beta-hydroxy-17 alpha-methyl-(3H)-estra-4,9,11-trien-3-one (R1881) (0.1 nM) stimulated cell growth by approximately 2.3 times. Increasing doses of R1881 (1-100 nM) partly decreased the stimulation of the cell growth. The anti-androgen cyproterone acetate exerted inhibitory effects on cell growth. The nuclear extract of the LNCaP-FGC cells contained 17,000 +/- 2,500 (mean +/- SD) KCl-extractable, nuclear androgen receptor sites/cell. Estrogen and progesterone receptors were not detectable in the nuclear extracts nor in cytosol, indicating that these receptors were absent. The release of proteins in the culture medium was studied using incorporation of the 35S-methionine, sodium dodecyl sulfate (SDS)-gel electrophoresis, and fluorography. Cells grown in media containing charcoal-stripped fetal calf serum released significantly lower amounts of a protein with an apparent molecular mass of 42,000 daltons. The release of this 42-kD protein could be restored in cells cultured in the presence of 5 alpha-dihydrotestosterone (0.1-1 microM) or R1881 (0.1-100 nM), whereas the addition of estrogens or corticosteroids had no effect. In the presence of anti-androgens, such as cyproterone acetate and 5,5-dimethyl-3-(4-nitro-3-(trifluoro-methyl)-phenyl)-2,4-imidasolidin edione, inhibitory effects on the release of the 42-kD protein were observed. The observed parallel between the effects of (anti)-androgens on the growth of the LNCaP prostate cells and the release of the 42-kD protein suggests that this protein is involved in the regulation of malignant prostate cell growth.
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PMID:Androgen-dependent growth regulation of and release of specific protein(s) by the androgen receptor containing human prostate tumor cell line LNCaP. 294 29

The transplantable human prostatic adenocarcinoma, PC-82, has been shown to be a suitable model for the study of several aspects of androgen-regulated tumor growth. This tumor contains an androgen receptor, and the purpose of the present investigation was to characterize this androgen receptor with respect to hormone specificity, sedimentation coefficient, dissociation constant, Stokes radius, ionic properties, and molecular mass. Cytosol was prepared from tumor tissues grown in athymic nude mice, which were castrated 10 days before harvesting the tumor. Scatchard plot analysis revealed a binding protein with a Kd of 0.1 nM for R1881 (methyltrienolone) and binding capacity of 120 fmol/mg protein. The receptor showed a high affinity for R1881, testosterone, and 5 alpha-dihydrotestosterone, respectively, whereas no or little affinity was found for progesterone and estradiol. In the presence of 10 mM molybdate the androgen receptor in PC-82 cytosol eluted from an FPLC anion exchange column (Mono Q) at 0.32 M NaCl, which is identical to what has been found for androgen receptors from rat prostate and calf uterine cytosol. Photoaffinity labeling of the [3H]R1881-androgen receptor complex and subsequent analysis on SDS-polyacrylamide gels resulted in a covalently labeled protein with a molecular mass of approximately 50 kD. The androgen receptor of the PC-82 tumor had a sedimentation coefficient of 4S and a Stokes radius of 3.3 nm at high ionic strength (0.4 M NaCl). It is concluded that the PC-82 tumor contains a binding protein with the properties described for androgen receptors present in prostate tissue.
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PMID:Characterization of androgen receptors in a transplantable human prostatic adenocarcinoma (PC-82). 295 63

Primary cell cultures from an androgen-dependent mouse mammary carcinoma, the Shionogi-SC 115 tumor, were cultured in the presence or absence of testosterone (50 nM). Characteristic changes in cellular morphology and cell growth were observed according to the presence or absence of the androgen. In testosterone-containing medium, cells formed individual clones, piling up one over another and showed no contact inhibition, whereas in the absence of the androgen, cells had a flattened morphology, they grew in a monolayer and cell multiplication was reduced. The testosterone-dependent changes were observed in culture as long as cells were maintained in androgen-containing medium. Only a few (3-5) days of culture in the absence of testosterone rendered cells irreversibly unresponsive to the androgen, and they could no longer produce tumours after inoculation in the host animal. Cellular proteins were analysed after culture in the presence or absence of testosterone. After [35S]methionine labelling of cells and SDS-PAGE of the cytosol, several proteins were specifically synthesized in the presence of testosterone, predominantly a 45 kD protein, which was not seen in the absence of the androgen. Conversely, a protein of 35 kD present in absence of the hormone disappeared in the presence of testosterone. The anti-androgen cyproterone acetate inhibited the characteristic cellular morphology, cell proliferation and protein synthesis observed in the presence of the the androgen. The antiprogestin and anti-glucocorticosteroid RU 486 also showed limited anti-androgen activity. The concentration of specific androgen receptor-binding sites did not change significantly after 3 months of culture with or without testosterone, i.e., in responsive and unresponsive cells.
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PMID:Testosterone-induced responsiveness to androgen in Shionogi mouse carcinoma cells. 295 18

Shionogi carcinoma 115 (SC115) had been accepted for 20 yr as an androgen-dependent mouse mammary tumor. However, we recently found that the growth of SC115 tumors in vivo is also stimulated by pharmacological doses of estrogen through estrogen receptor. In the present study, action mechanisms of androgen or high doses of estrogen in the growth stimulation of SC115 were examined using a cloned cell line (SC-3) derived from the SC115 tumor. In serum-supplemented [2% steroid-free fetal calf serum-Eagle's minimum essential medium (MEM)] and serum-free [HAM F-12: MEM (1:1, v/v) containing 0.1% bovine serum albumin] media, testosterone (Test, 10(-9)-10(-6) M) significantly increased both cell number and DNA synthesis of SC-3 cells (by up to 10-fold), whereas oestradiol-17 beta (10(-12)-10(-6) M) had no such effects; the Test-induced growth was completely inhibited by the addition of a 100-fold molar excess of cyproterone acetate (CA). The serum-free medium cultured with SC-3 cells in the presence or absence of 10(-8) M Test was collected [conditioned medium (CM) or conditioned medium without Test (CM-)], and then Test in CM was removed by Gel filtration using Sephadex G-100 or inactivated by the addition of a 100-fold molar excess of CA. In the serum-free culture system, the addition of the CM without Test activity significantly enhanced both number of SC-3 cells and DNA synthesis in the cells, whereas CM(-) had no such effects. The present findings suggest that growth-stimulatory activities of androgen and high doses of estrogen on SC115 cells are mediated by growth factor(s), secreted from SC115 cells through androgen receptor and from some of nontransformed cells through estrogen receptor, respectively.
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PMID:Action mechanisms of physiological doses of androgen or pharmacological doses of estrogen in growth stimulation of Shionogi carcinoma 115 in mice. 296 36

Since there is convincing evidence for a role of adrenal steroids as precursors of active sex steroids in peripheral tissues, especially prostate cancer, we have studied the effect of the four main adrenal steroids, namely dehydroepiandrosterone sulfate (DHEA-S), DHEA, 5-androstene-3 beta,17 beta-diol (delta 5-diol) and 4-androstene-3,17-dione (delta 4-dione) on the growth of an androgen-sensitive clone (SEM-1) of the mouse mammary carcinoma Shionogi. From a control doubling time of 6.69 +/- 0.03 days, 0.1 microM DHT, 1.0 microM delta 4-dione, 10 microM delta 5-diol, 10 microM DHEA-S and 10 microM DHEA decreased generation time to 1.60 +/- 0.01, 1.69 +/- 0.01, 1.95 +/- 0.01, 4.37 +/- 0.02 and 5.66 +/- 0.03 days, respectively (P less than 0.01 vs. control). The same compounds exerted their stimulatory effects on cell growth at the following ED50 values: 0.06 nM, 16 nM, 90 nM, 150 nM and 16 microM for DHT, delta 4-dione, DHEA, delta 5-diol and DHEA-S, respectively. The stimulatory effect of all compounds was inhibited in a competitive manner by the pure antiandrogen hydroxyflutamide. Further evidence for an action of the adrenal steroids through the androgen receptor is indicated by competition of [3H]testosterone uptake in the tumor cells at the following IC50 values: 0.21 nM, 0.63 nM, 50 nM, 75 nM and 680 nM for DHT, testosterone, delta 4-dione, delta 5-diol and DHEA, respectively. The present data show that the four main adrenal steroids present in the serum of adult men can exert potent stimulatory effects on the growth of an androgen-sensitive cancer cell line through an androgen receptor-mediated mechanism.
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PMID:Adrenal precursor C19 steroids are potent stimulators of growth of androgen-sensitive mouse mammary carcinoma Shionogi cells in vitro. 297 15

The androgen receptor content of normal human liver, hepatocellular carcinoma, and surrounding liver tissue was determined in patients with chronic liver disease. Androgen receptor was detected in all six normal livers obtained from 4 men and 2 women. The androgen receptor content in these 6 individuals ranged from 5.0 to 10.2 fmol/mg protein (Kd 10.6-31.8 X 10(-10) M). The livers from 2 patients with chronic active hepatitis and from 10 cirrhotic patients with hepatocellular carcinoma had detectable amounts of androgen receptor ranging from 2.0 to 14.8 fmol/mg protein (Kd 4.0-30.9 X 10(-10) M). Androgen receptor was found in the cytosol of 14 of 19 men with hepatocellular carcinoma. The titer ranged from 3.7 to 45.4 fmol/mg protein (Kd 3.2-21.4 X 10(-10) M). Hepatocellular carcinoma had a significantly higher concentration of androgen receptor than did the surrounding cirrhotic liver tissue. In 2 men and 1 woman, androgen receptor was detected in the cirrhotic liver but not in the tumor. In the remaining 3 men, both tumor and cirrhotic liver were negative for androgen receptor.
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PMID:Androgen receptors in hepatocellular carcinoma and surrounding parenchyma. 299 Oct 72

Leuprolide, a synthetic LHRH analog, inhibited growth of the Dunning R 3327 androgen-sensitive rat prostatic tumor and induced weight loss in male accessory sex organs. The relationship between the mode of administration and efficiency of the treatment was examined. Maintenance of the drug level in vivo seemed to be one of the important factors in the suppression of tumor growth, while a decrease in the weight of the accessory sex organs was mainly dependent on the dose administered. No treatment with leuprolide surpassed the effect caused by castration. Cytosolic androgen receptor and acid phosphatase activity in the tumor tissues were not changed significantly after treatment with leuprolide.
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PMID:Effect of leuprolide on growth of rat prostatic tumor (R 3327) and weight of male accessory sex organs. 313 78


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