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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of androgen receptor messenger RNA in hepatocellular carcinomas and hepatoma cell lines was studied using Northern-blot analysis and the complementary DNA-polymerase chain reaction method. Androgen receptor messenger RNAs were detected (although in low levels) in both hepatocellular carcinoma tissues and noncancerous tissues of the liver in all eight cases we studied, except for the tumor sample of one case. None of the hepatoma cell lines studied, however, expressed detectable levels of androgen receptor messenger RNA except for the SK-HEP-1 hepatoma cell line.
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PMID:Expression of androgen receptor mRNA in human hepatocellular carcinomas and hepatoma cell lines. 164 43

Sex hormones have been shown to influence the development and course of several liver diseases. The worldwide predominance of hepatocellular carcinoma (HCC) in males has led to the suggestion that this disease might be hormone-responsive. Therefore, the hepatic estrogen (ER) and androgen receptor (AR) status of liver specimens from such patients was investigated. Samples were obtained from three female and six males patients undergoing liver resection; in each case, a small sample of both the tumor and adjacent normal tissue was collected. All patients had primary hepatocellular carcinoma without cirrhosis. In most cases, the tumor and the normal specimen had an equivalent content of cytosolic ER; however, three of the tumor samples (one female and two male) displayed considerably elevated cytosolic ER levels as compared to that of the normal tissue. In every sample, the tumor contained less nuclear ER than did the normal liver. When AR was measured, tumors of three patients (one female and two male) demonstrated a twofold elevation in cytosolic AR as compared to adjacent normal tissue. In the two male patients, an approximately twofold greater nuclear AR was found. Two other samples from male patients showed a modest elevation of cytosolic AR in the tumors. The patients whose tumors showed elevations in ER were not the same patients as those in whom the AR was elevated. Thus, these studies indicate that certain, but not all, specimens of HCC demonstrate either elevated ER or AR and suggest that a determination of receptor content might be useful prior to initiation of certain antihormone therapies.
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PMID:Quantitation of estrogen and androgen receptors in hepatocellular carcinoma and adjacent normal human liver. 165 43

The specificity of androgen receptor in hepatocellular carcinoma and the liver was investigated using auto-radiographic techniques. Partial hepatectomy was carried out on 11 patients with hepatocellular carcinoma and associated parenchymal disease of the liver. Androgen receptors were assayed biochemically for hepatocellular carcinoma and the surrounding liver in all cases. Estrogen receptor was also measured in five patients. In eight patients, fresh resected specimens as thick as 3 mm were first incubated for 15 minutes in a medium containing estradiol and hydrocortisone, and then radio-labeled testosterones were added to the medium. After another 60 minutes incubation, macro-autoradiographic studies were carried out. With the same medium and chemicals, and using the same principle, micro-autoradiographic studies were performed using fresh hepatocellular carcinoma and liver cell suspensions in six cases. The radio-labeled testosterones were incorporated into hepatocellular carcinoma and the liver to a parallel extent with the androgen receptor titers biochemically assayed. The current results seem to indicate that androgen receptors present in hepatocellular carcinoma and the liver of humans specifically bind androgens. Further studies are needed to elucidate the role of AR in hepatocarcinogenesis in humans.
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PMID:Specificity of androgen receptors of hepatocellular carcinoma and liver in humans. 217 26

The effects of androgen withdrawal and replacement on the concentrations of androgen receptor (AR) protein and AR mRNA were investigated in rat ventral prostate and seminal vesicles and in cultured human hepatoma (HepG2) cells. AR mRNA concentrations were determined by Northern blotting with single stranded AR cRNA as the hybridization probe, whereas antibodies raised against two synthetic 17-amino acid long peptides corresponding to the N-terminal and steroid-binding regions of the AR were employed in immunological receptor assays. AR mRNA levels in both prostate and seminal vesicles increased about 2-fold within 24 h after castration and continued to rise within the next 48 h to values that were 9- to 11-fold higher than those in intact controls. Administration of pharmacological doses of testosterone (400 micrograms steroid/day) to 1-day castrated animals for 24-48 h brought about a decrease in AR mRNA levels in accessory sex organs to levels in intact controls. Similar results were obtained in cultured HepG2 cells where a switch to serum- and steroid-free medium elicited a rapid increase (approximately 4-fold in 10 h) in the AR mRNA level, which was prevented by inclusion of 10(-7) M testosterone in culture medium. Similar, but quantitatively less marked, changes occurred in the AR protein concentration in prostate, seminal vesicles, and HepG2 cells, as determined by immunoblotting using antibodies against AR peptides. In addition, immunohistochemical studies showed that AR is a nuclear protein of the prostatic epithelial cells in both intact and castrated rats, and suggested that short term castration increases the concentration of nuclear AR in the prostate. Taken together, these data indicate that androgens down-regulate the concentration of AR protein and AR mRNA in a variety of target tissues.
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PMID:Regulation of androgen receptor protein and mRNA concentrations by androgens in rat ventral prostate and seminal vesicles and in human hepatoma cells. 217 37

Both estrogens and androgens have been shown to stimulate sex hormone binding globulin (SHBG) secretion in vitro in the hepatocellular carcinoma cell line, Hep G2, in contrast to the expected inhibition by androgens from in vivo studies. However, such in vitro stimulation was only demonstrated at high steroid doses, generally in serum-containing medium, with added Phenol Red. In the present study, Hep G2 cells were grown in serum-free medium, without Phenol Red, under the influence of testosterone (T) (0, 0.5-500 nM) and ethinyl estradiol (EE2) (0, 50 pM-500 nM). Levels of secreted SHBG and albumin were correlated with androgen receptors in cytosolic (ARc) and nuclear (ARn) fractions and with DNA levels. In the presence of increasing T levels, SHBG levels fell to 39% of control values at 5 nM T (P = 0.047), rising to 97% of control at 500 nM. Conversely, incubation with EE2 produced a rise in SHBG secretion of more than 100% at 0.5 nM (P less than 0.02) which was sustained to 50 nM (P less than 0.005). DNA levels did not change with the addition of testosterone or EE2, with the exception of a 15% reduction at 5 nM EE2 (P less than 0.05). Albumin levels in the medium were not significantly altered by either steroid. However, in response to T, androgen receptor (AR) levels were reduced in cytosolic (42% of control) and nuclear (22%) fractions at 5 nM, and these changes in ARc and ARn correlated with SHBG levels over the range of T concentrations (P = 0.04 and P = 0.017, respectively). Nuclear estrogen receptor (ER) increased over 10-fold at 5 and 50 pM EE2 (P less than 0.001) and maintained 50 nM (P less than 0.001). Cytosolic ER was reduced at 0.5 and 5 nM but recovered at 50 nM, correlating with SHBG levels (P less than 0.001). These findings are consistent with the hypothesis that estrogens and androgens regulate SHBG synthesis in man by direct, specific, probably receptor-mediated effects on hepatocytes. Hep G2 cells grown in serum-free medium are a suitable experimental system for further study of this phenomenon.
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PMID:Estrogen and androgen regulation of sex hormone binding globulin secretion by a human liver cell line. 227 57

The reported presence of androgen receptors (AR) in hepatocellular carcinoma (HCC) and foetal liver, but not in normal adult human liver, has been followed by further study of AR employing a new microassay. Tissues examined were: 5 samples of HCC with surrounding normal liver in 3 cases; 5 samples of cirrhotic liver and a single specimen of HCC in a child. High affinity binding of 5 alpha-dihydrotestosterone (DHT) was detected in cytosol (11.5-21 fmol/mg, Kd 1.5 X 10(-10)-3.1 X 10(-11) mol/l) and in nucleosol (8.7-11.4 fmol/mg, 6.7-1.4 X 10(-11) mol/l) of the 5 HCC samples. All other liver samples exhibited non-specific binding only. Competition studies indicated that DHT, testosterone, androstenedione, 5 alpha-androstan-3 beta, 17 beta-diol, androst-5-ene-3 beta,17 beta-diol and cyproterone acetate were acting at the same receptor binding site, relative displacement of 3H-DHT being 100, 85.7, 77.4, 67.8, 34.5 and 60.2 per cent respectively. Presence of 3.5S cytosolic and both 2.8S and 4S nucleosolic receptor patterns were demonstrated in both prostatic and HCC tissue. These studies confirm the presence of a cytosolic and nucleosolic androgen receptor in HCC which possesses similar characteristics to the AR of human prostate.
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PMID:Characterisation of high affinity binding sites of androgens in primary hepatocellular carcinoma. 241 40

The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.
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PMID:Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy. 259 Mar 84

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

Both androgen and estrogen receptors were studied in human hepatocellular carcinoma and noncancerous liver tissue surrounding it. Androgen receptor was detected in the cytosol and/or nucleosol of 4 of 8 cancerous tissues and 1 of 6 noncancerous tissues. The levels of androgen receptor in hepatocellular carcinomas ranged from 3.4 to 37.6 fmoles per mg protein with dissociation constants (Kd) of 0.226 - 51.3 X 10(-9) M. That in the surrounding noncancerous tissue was 2.1 fmoles per mg protein with Kd of 0.941 X 10(-9) M. Estrogen receptor was detected in the cytosol of 1 of 7 cancerous tissues, while it was detected in the cytosol and/or nucleosol of 3 of 7 noncancerous tissues. The level of estrogen receptor in hepatocellular carcinoma was 4.9 fmoles per mg protein with Kd of 1.20 X 10(-9) M, and those in the surrounding noncancerous tissues ranged from 2.6 to 1,073 fmoles per mg protein with Kd of 0.223 - 3.15 X 10(-9) M. The results suggest that the expression of androgen receptor may be augmented in association with malignant transformation of hepatocytes while the expression of estrogen receptor may be rather suppressed and that some of hepatocellular carcinomas may be androgen-dependent.
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PMID:Androgen and estrogen receptors in hepatocellular carcinoma and in the surrounding noncancerous liver tissue. 301 31

This study investigated the relationship between liver tumor development and androgen-receptor expression in diethylnitrosamine hepatocarcinogenesis in Wistar rats (SUAH substrain). Random liver samples were assayed by an isoelectric focusing method, with [3H]mibolerone as androgenic radioligand. After 16 wk of oral diethylnitrosamine treatment there was a greater than 20-fold increase in hepatic androgen receptor concentration in female rats (control group 0.3 +/- 0.07 fmol/mg cytosol protein; test group 8.36 +/- 0.96 fmol/mg cytosol protein; p less than 0.001, unpaired Student's t-test). This coincided with, and may be related to, an accelerated development of neoplastic nodules or hepatocellular carcinoma, or both. Male rats showed slower tumor development and no change in androgen receptor concentrations. This model is the first to demonstrate significantly increased androgen sensitivity in experimental hepatic carcinogenesis analogous to increased androgen receptor expression in human hepatocellular carcinoma. It may provide insight into steroid hormone sensitivity in developing tumors, and a means of testing potential therapeutic use of hormonal manipulation in human liver cancer.
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PMID:Increased hepatic androgen receptor expression in female rats during diethylnitrosamine liver carcinogenesis. A possible correlation with liver tumor development. 335 Feb 89


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