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Overexpression of hepatocyte nuclear factor‐3α induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells
Author(s) -
Lee Hyun Joo,
Chattopadhyay Soma,
Yoon WanHee,
Bahk Jong Yoon,
Kim TaeHyoung,
Kang Hyung Sik,
Lee Keesook
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21069
Subject(s) - prostate cancer , apoptosis , cancer research , programmed cell death , biology , downregulation and upregulation , cancer cell , prostate , cancer , microbiology and biotechnology , medicine , gene , biochemistry
BACKGROUND Hepatocyte nuclear factor‐3α (HNF‐3α) has been known to act as a repressor in the pathogenesis of many cancers. Herein, we investigated the effect of HNF‐3α overexpression in prostate cancer cells. METHODS HNF‐3α was overexpressed in prostate cancer cells using an adenovirus recombinant expressing wild‐type HNF‐3α. The apoptosis of prostate cancer cells was determined by TUNEL, FACS, and caspase activity analyses. RESULTS Adenovirus‐mediated overexpression of HNF‐3α caused cell death in prostate cancer cells as assessed by changes in cellular and nuclear morphology, TUNEL analysis, and caspase activations. Furthermore, FACS analysis showed an increased sub‐G1 phase of cell cycle as well as the G2/M phase with a corresponding decrease in S phases. HNF‐3α overexpression caused the upregulation of p53 protein and its accumulation, together with HNF‐3α, in the cytoplasm. It also causes Bax protein to localize to the mitochondria‐enriched fraction. These findings suggest that multiple apoptotic pathways seem to be involved in the HNF‐3α‐induced cell death: pathways involving the accumulation of p53 protein in the cytoplasm and subsequent cytochrome c release, and other pathways involving death receptor signaling and caspase‐8 activation. CONCLUSIONS The results of the current study suggest a novel function of HNF‐3α as a killer of malignant prostate cancer cells, which reveals HNF‐3α as a promising therapeutic molecule for prostate cancers. Prostate 70: 353–361, 2010. © 2009 Wiley‐Liss, Inc.