Journal Article

SHORT COMMUNICATION: Identification of genes whose expression is altered during mitosuppression in livers of ethinyl estradiol-treated female rats

Jinqiang Chen, David A. Schwartz, Thayer A. Young, James S. Norris and James D. Yager

in Carcinogenesis

Volume 17, issue 12, pages 2783-2786
Published in print December 1996 | ISSN: 0143-3334
Published online December 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.12.2783
SHORT COMMUNICATION: Identification of genes whose expression is
                    altered during mitosuppression in livers of ethinyl estradiol-treated female
                    rats

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In this study, our goal was to identify genes whose expression in liver is altered in female F-344 rats during mitosuppression induced by 42 days of ethinyl estradiol (EE) treatment (Yager et al., Carcinogenesis, 15, 2117-2123, 1994). Northern analysis demonstrated that the mRNA levels for transforming growth factor-β1 (TGF-β1)and the mannose 6-phosphate/insulin-like growth factor II receptor were significantly increased by EE treatment. Ten cDNA clones representing mRNAs whose expression was increased two- to four-fold in the mitosuppressed livers were identified by differential display. Sequence analysis revealed that one was homologous to the S-24 ribosomal protein and another to mitochondrial ATPase subunit e. The remaining clones showed no homology to known genes in GenBank. However, the expression of clones 15, 16 and 17 was increased in HepG2 cells following treatment with doxorubicin suggesting their induction by oxidative DNA damage. These results suggest that two independent but interrelated signalling pathways, one mediated through transforming growth factor-β and the other through oxidative DNA damages, may contribute to hepatic mitosuppression caused by EE, perhaps through activation of cyclin-dependent kinase inhibitors.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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