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Transcription Factor POU6F1 Is Important for Proliferation of Clear Cell Adenocarcinoma of the Ovary and Is a Potential New Molecular Target
  1. Nao Suzuki, MD, PhD*,
  2. Norihito Yoshioka, MD*,
  3. Atsushi Uekawa, PhD*,
  4. Noriomi Matsumura, MD, PhD,
  5. Akiko Tozawa, MD, PhD*,
  6. Jyunki Koike, MD, PhD,
  7. Ikuo Konishi, MD, PhD,
  8. Kazushige Kiguchi, MD, PhD* and
  9. Bunpei Ishizuka, MD*
  1. *Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Kanagawa;
  2. Department of Obstetrics and Gynecology, School of Medicine, Kyoto University, Kyoto; and
  3. Department of Pathology, St Marianna University School of Medicine, Kanagawa, Japan.
  1. Address correspondence and reprint requests to Nao Suzuki, MD, PhD, Department of Obstetrics and Gynecology, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. E-mail: nao{at}marianna-u.ac.jp.

Abstract

Objective: Clear cell adenocarcinoma of the ovary often shows resistance to anticancer agents. It accounts for 20% of epithelial ovarian cancer in Japan versus around 5% in other countries. We investigated new molecules to use when developing molecular-targeting therapy for clear cell adenocarcinoma.

Methods: Reverse transcriptase polymerase chain reaction and Western blot analysis were performed to confirm the expression of POU6F1 in several kinds of cell lines derived from epithelial ovarian carcinoma. Microarray analyses were performed using 2 ovarian cancer microarray data sets available on the Internet. Immunohistochemical staining was also done to confirm both the expression and the localization of POU6F1 using human ovarian epithelial ovarian carcinoma tissue specimens. In addition, the gene cluster located downstream of transcription factor POU6F1 was investigated to analyze its role in the proliferation of clear cell adenocarcinoma of the ovary via the lysophosphatidic acid receptor, a G protein-coupled receptor. Furthermore, RNA interference studies with small interfering RNA (siRNA) were performed to assess the effect of POU6F1 on proliferation of xenograft tumors after injection of clear cell adenocarcinoma cells into nude mice.

Results: Expression of POU6F1 at messenger RNA and protein was confirmed in cell lines derived from epithelial ovarian carcinoma. The microarray analyses performed using the 2 ovarian cancer microarray data sets available on the Internet indicated that POU6F1 expression was significantly greater in clear cell adenocarcinoma. Immunostaining confirmed the nuclear localization of POU6F1 in clear cell adenocarcinoma (100%). Exposure to the siRNA for POU6F1 reduced the expression of lysophosphatidic acid receptors, which are G protein-coupled receptors involved in tumor cell proliferation. POU6F1 siRNA dose-dependently suppressed the proliferation of clear cell adenocarcinoma cell lines, and a similar effect was confirmed for tumors transplanted into nude mice.

Conclusions: Clear cell adenocarcinoma shows little response to standard therapy. The results of this study suggested that the transcription factor POU6F1 could be a new molecular target for treatment of this cancer.

  • Clear cell adenocarcinoma of the ovary
  • POU6F1
  • Cell proliferation
  • Lysophosphatidic acid
  • Molecular-targeting therapy

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Footnotes

  • This research was supported by a grant for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 19390430; N.S.). All authors have no conflicts of interest to declare.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.ijgc.com).

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