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

Abstract:

: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-beta1 (TGF-beta1) 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-beta and the other through oxidative DNA damage, may contribute to hepatic mitosuppression caused by EE, perhaps through activation of cyclin-dependent kinase inhibitors.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Chen J,Schwartz DA,Young TA,Norris JS,Yager JD

doi

10.1093/carcin/17.12.2783

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

2783-6

issue

12

eissn

0143-3334

issn

1460-2180

journal_volume

17

pub_type

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