Role of sex steroid receptors in pathobiology of hepatocellular carcinoma
Open accessAbstract
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 ERalpha alone until 1996 when ERbeta 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.
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Androgens play a crucial role in the development of hepatocellular carcinoma.
“androgens have been shown to play a crucial role in the development of hepatocellular carcinoma (Kalra et al., 2008, Kanda et al., 2014).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Kalra et al., 2008
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Intracrine androgen biosynthesis, metabolism and action revisited
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“, 2015) and androgens have been shown to play a crucial role in the development of hepatocellular carcinoma (Kalra et al., 2008; Kanda et al., 2014).”
5α-Reductase Type 2 Regulates Glucocorticoid Action and Metabolic Phenotype in Human Hepatocytes
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Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model
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- Authors
- Kalra, M., Mayes, J., Assefa, S., Kaul, A. K., & Kaul, R.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Kaul, Rashmi
- ORCID
- Kaul, Rashmi
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2008
- Volume
- 14
- Issue
- 39
- Pages
- 5945
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC2760195
- OpenAlex
- W2153047557
- Cited by
- 141
- References
- 162
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 9 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 4 · 2017: 15 · 2016: 7 · 2015: 15 · 2014: 6 · 2013: 11 · 2012: 10
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- hepatocellular carcinoma, sex steroid receptors, estrogen receptor alpha, estrogen receptor beta, androgen receptor, sex hormones, hormone therapy, liver cancer pathogenesis, viral hepatitis, hepatoma cells
- MeSH terms
- Androgens, Animals, Disease Models, Animal, Estrogens, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Receptors, Androgen, Receptors, Estrogen, Sex Characteristics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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