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Estrogen's Effects on Mitochondrial Gene Expression: Mechanisms and Potential Contributions to Estrogen Carcinogenesis
Author(s) -
CHEN JINQIANG,
YAGER JAMES D.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.030
Subject(s) - estrogen receptor , estrogen receptor beta , biology , estrogen , estrogen receptor alpha , microbiology and biotechnology , mitochondrion , gper , western blot , gene expression , gene , endocrinology , biochemistry , genetics , cancer , breast cancer
A bstract : Estrogen receptor (ER)α and ERβ are localized in the nucleus and involved in the regulation of nuclear estrogen‐responsive genes by 17β estradiol (E2). In addition, recently others have shown that upon E2 binding, ERα localizes to the plasma membrane and initiates mitogen‐activated protein kinase (MAPK)‐mediated signal transduction. Previously, we reported that in liver, cultured rat hepatocytes and human HepG2 cells, estrogen treatment enhanced mitochondrial DNA (mtDNA)‐encoded gene transcript levels. These effects were blocked by a specific antiestrogen, suggesting a role for the ER. Others have reported the presence of putative estrogen‐responsive elements in mtDNA. These observations suggested the hypothesis that the ER localized in mitochondria and functioned directly to enhance the levels of mtDNA‐encoded transcripts, analogous to what has been observed for the glucocorticoid hormone receptor. Using Western blot analysis, confocal immunofluorescence, immunogold electron microscopy, and gel electrophoresis mobility shift assays, we have demonstrated the estrogen‐dependent presence of ERβ and ERα within mitochondria of HepG2 and MCF‐7 human breast tumor cells. Together, these results suggest that the ERs may act as transcription factors directly involved in the regulation by E2 of mtDNA transcription.