Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma.

Abstract

Of all of the epithelial ovarian cancers, clear cell carcinoma (CCC) of the ovary has the worst prognosis. We applied the oligonucleotide array technique to identify genes generally involved in CCC. Of the approximately 12,600 genes that were analyzed, 28 were expressed significantly differently between four CCC and seven non-CCC cell lines. Among 16 up-regulated genes in CCC, we further investigated a transcription factor, hepatocyte nuclear factor-1 beta (HNF-1 beta). We validated up-regulation of HNF-1 beta in CCC in terms of both mRNA and protein level using real-time quantitative reverse transcriptase-polymerase chain reaction and immunoblotting. Immunohistochemical analysis of 83 surgically resected ovarian cancers showed that almost all CCC specimens (21 of 22 cases) had nuclear staining for HNF-1 beta, whereas most non-CCC specimens (60 of 61 cases) showed no immunostaining or only focal and faint staining in the nucleus. Furthermore, we investigated the significance of HNF-1 beta expression in CCC using RNA interference. The reduction of HNF-1 beta expression by RNA interference induced apoptotic cell death in ovarian CCC cells, which was confirmed by terminal dUTP nick-end labeling and fluorescence-activated cell-sorting analyses. Our results suggest that HNF-1 beta is not only an excellent CCC-specific molecular marker but also a molecular target for therapy of ovarian CCC.

• Authors: Akira Tsuchiya, Michiie Sakamoto, Jun Yasuda, Makoto Chuma, Tsutomu Ohta, Misao Ohki, Toshiharu Yasugi, Yuji Taketani, Setsuo Hirohashi
• Journal: The American journal of pathology (Am J Pathol) Vol. 163 Issue 6 Pg. 2503-12 (Dec 2003) ISSN: 0002-9440 [Print] United States
• PMID: 14633622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• HNF1B protein, human
• RNA, Messenger
• Transcription Factors
• Hepatocyte Nuclear Factor 1-beta

Topics

• Adenocarcinoma, Clear Cell (genetics, metabolism, physiopathology, therapy)
• Apoptosis
• Biomarkers, Tumor (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Female
• Gene Expression Profiling
• Hepatocyte Nuclear Factor 1-beta
• Humans
• Immunohistochemistry
• Middle Aged
• Ovarian Neoplasms (genetics, metabolism, physiopathology, therapy)
• RNA Interference
• RNA, Messenger (metabolism)
• Transcription Factors (antagonists & inhibitors, genetics, metabolism)