Hepatomas: Hormone receptors and therapy

Friedman, Michael; Demanes, D. Jeffrey; Hoffman, Philip G.

doi:10.1016/0002-9343(82)90728-8

Cited by 68 publications

(16 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of similar levels of ER in both normal and malignant liver tissue is in agreement with a previous study of liver cytosols (Friedman, 1982), where partial, short-term remission in two female patients was reported following progestagen therapy. However, the presence of AR in malignant and foetal, but not in normal adult liver tissue does point to the possibility that HCC may be an androgen-responsive tumour; further work is required to establish the precise rple of sex-steroids in this disease.…”

Section: Discussionsupporting

confidence: 92%

“…Duffy & Duffy (1978) were the first to demonstrate ER in normal human liver cytosol. Of further interest in relation to tumour formation is their presence in hepatic adenoma, demonstrated by McDonald et al (1978), and in HCC cytosol, shown by Molteni et al (1979) and Friedman et al (1982). The latter workers, however, showed no difference in ER levels between HCC and surrounding normal liver tissue.…”

mentioning

confidence: 94%

See 1 more Smart Citation

Sex steroid receptor proteins in foetal, adult and malignant human liver tissue

Iqbal¹,

Wilkinson²,

Pj³

et al. 1983

Br J Cancer

View full text Add to dashboard Cite

Summary Sex steroid receptor proteins were studied in human normal liver and hepatocellular carcinoma (HCC). Oestrogen receptor (ER) was detected in nucleosol and cytosol of 4 normal adult and 5 malignant liver specimens and in the cytosol of 6 foetal liver samples. Levels were 27.6-500 fmol mg 1 soluble protein in normal adults (Kd 1.48 x l0-8-l.l2 x 1010moll-1), 45-290fmolmg-1 in malignant liver tissue (Kd 3.26x 10-9-3.64x 10-'moll-1) and a mean of 93fmolmg-1 in foetal tissue (Kd 1.55x lO-9moll-P). Androgen receptors (AR) were found only in cytosol and nucleosol of HCC (23-370fmolmg-1) and in cytosol from foetal liver (29fmolmg-1) with Kd from 2.90x l0-9 to 3.734x 1010moll-1. AR was distinguished from sex hormone binding globulin, which was also present in all cytosol samples, by the former's ability to selectively bind to methyltrienolone and the latter's absence from nucleosol. These findings provide further support for suggestions that oestrogen-related hepatic functions in man may be mediated by receptors and raise the possibility that hepatocellular carcinoma may be androgen dependent.

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 94%

Sex steroid receptor proteins in foetal, adult and malignant human liver tissue

Iqbal¹,

Wilkinson²,

Pj³

et al. 1983

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…35 36 Several groups have shown the presence of oestrogen receptors in HCC specimens as well as in adjacent normal human liver. [37][38][39] The data suggested that oestrogen receptor levels were lower in HCC samples than in normal liver, but the diVerences reported were not significant. 38 However, it is diYcult to correlate or compare the data from these various reports because of the limited numbers of human tumours examined, and the wide range of binding values obtained in each study.…”

Section: -32mentioning

confidence: 90%

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats

Shimizu¹,

Yasuda²,

Mizobuchi³

et al. 1998

European Journal of Gastroenterology & Hepatology

View full text Add to dashboard Cite

Aims-To examine the eVects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis. Methods-Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay. Results-Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level. Conclusion-These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.

show abstract

“…In 1978, Duffy and Duffy first reported the presence of ER in normal human liver [28] . Subsequently, the presence of ERs in human HCC was demonstrated by Molteni et al [29] followed by Friedman et al [30] and Iqbal et al [31] . Since then, a number of studies have been reported addressing the expression of ERs in normal as well as neoplastic liver tissues.…”

Section: Estrogen Receptormentioning

confidence: 99%

“…The early studies used indirect methods of receptor detection based on ligand binding assays. Table 1 gives the details of these studies [13,15,17,[30][31][32][33][34][35][36][37] . These assays were quantitative and measured the amount of receptor in the samples as well as its affinity for the ligand in terms of dissociation constants.…”

Section: Estrogen Receptormentioning

confidence: 99%

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

Kalra¹,

Mayes²,

Assefa³

et al. 2008

WJG

133

116

View full text Add to dashboard Cite

The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro , in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

show abstract

Hepatomas: Hormone receptors and therapy

Cited by 68 publications

References 24 publications

Sex steroid receptor proteins in foetal, adult and malignant human liver tissue

Sex steroid receptor proteins in foetal, adult and malignant human liver tissue

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

Contact Info

Product

Resources

About