Schlott, T. and Thasler, W. and Gorzel, C. and Pahernik, S. and Brinck, U. and Eiffert, H. and Droese, M. (2002) Detection of MDM2 alterations in cultured human hepatocytes treated with 17 beta-estradiol or 17 alpha-ethinylestradiol. ANTICANCER RESEARCH, 22 (3). pp. 1545-1551. ISSN 0250-7005, 1791-7530
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Background: Preneoplastic and neoplastic lesions of the liver are suspected to arise as a result of estrogen treatment. Here we present the first report on the modulational effects of the steroids 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) on oncogene MDM2 in human hepatocytes. Materials and Methods:. Collagen-embedded cultures of hepatocytes stimulated with different E2/EE2 concentrations were analyzed by immunocytoehemistry, RT-PCR and sequencing for MDM2 protein/ mRNA expression, MDM2 mRNA splicing and MDM2 gene mutation. Results: The hepatocytes responded to stimulation with steroid E2/EE2 concentrations from 1-100 nmol/l with the overexpression of MDM2 protein while non-stimulated cells were negative. Stimulation with 1 nmol/l E2 and 10-100 nmol/l EE2 induced MDM2 splicing variants. Hepatocytes treated with 100 nmol/l E2 contained full-length MDM2 mRNA carrying a new type of MDM2 gene mutation. Unstimulated hepatocytes revealed neither mRNA splicing nor alteration of the MDM2 genes. Conclusion: The data show that steroid hormones are involved in the induction of MDM2 alterations in benign human hepatocytes. We speculate that some of the alterations may influence MDM2 function, thus possibly favouring genesis of liver changes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | WILD-TYPE P53; HEPATOCELLULAR-CARCINOMA; DNA-ADDUCTS; IN-VITRO; C-MYC; GENE; EXPRESSION; ONCOPROTEIN; PROTEIN; HEPATOCARCINOGENESIS; MDM2; 17 beta-estradiol; 17 alpha-ethinylestradiol; hepatocytes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2021 12:41 |
| Last Modified: | 26 Oct 2021 12:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40281 |
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