This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Masuyama, H. Articles by Kudo, T. Search for Related Content PubMed PubMed Citation Articles by Masuyama, H. Articles by Kudo, T.

Expression and Potential Roles of Pregnane X Receptor in Endometrial Cancer

Department of Obstetrics and Gynecology, Okayama University Medical School, Okayama, 700-8558, Japan

Address all correspondence and requests for reprints to: Hisashi Masuyama, M.D., Ph.D., Department of Obstetrics and Gynecology, Okayama University Medical School, 2-5-1, Shikata, Okayama, 700-8558, Japan. E-mail: masuyama{at}cc.okayama-u.ac.jp.

Estrogen has been shown to contribute greatly to growth and development in endometrial cancer. And recent research has suggested that intratumoral production of estrogen may play important roles in this cancer tissue. On the other hand, pregnane X receptor (PXR), a new member of nuclear receptors, has been shown to mediate the genomic effects of steroid hormones, including estrogen and xenobiotics. And this receptor is thought to regulate the expression of the cytochrome P-450 3A (CYP3A) gene family, which plays important roles in the metabolism of endogenous steroids and xenobiotics. Various levels of PXR expression were found in endometrial cancer tissues but not normal tissues. Tissues showing high PXR expression showed significantly high expression of CYP3A4/7 and low expression of estrogen receptor (ER) compared with levels in tissues showing low PXR expression. In endometrial cancer cell lines, HEC-1 cells, which express high PXR and low ER and progesterone receptor, show a stronger transcriptional response of the PXR-CYP3A pathway to the PXR ligands, especially endocrine-disrupting chemical, than do Ishikawa cells. These data suggest that the steroid/xenobiotics metabolism in the tumor tissue through PXR-CYP3A pathway might play an important role, especially in alternative pathway for gonadal hormone and endocrine-disrupting chemical effects on endometrial cancer expressing low ER.

This work was supported, in part, by research grants (14042236, 14571562) from the Ministry of Education, Science and Culture of Japan (to H.M.).

Abbreviations: CAT, Chloramphenicol acetyl transferase; CYP3A, cytochrome P-450 3A; DDT, dichlorodiphenyltrichloroethane; E2, 17ß-estradiol; EDC, endocrine-disrupting chemical; EIA, enzyme immunoassay; ER, estrogen receptor; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; P, progesterone; PR, P receptor; PXR, pregnane X receptor.

This article has been cited by other articles:

				D. Gupta, M. Venkatesh, H. Wang, S. Kim, M. Sinz, G. L. Goldberg, K. Whitney, C. Longley, and S. Mani Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer Clin. Cancer Res., September 1, 2008; 14(17): 5332 - 5340. [Abstract] [Full Text] [PDF]

				R. Callaghan, E. Crowley, S. Potter, and I. D. Kerr P-glycoprotein: So Many Ways to Turn It On J. Clin. Pharmacol., March 1, 2008; 48(3): 365 - 378. [Abstract] [Full Text] [PDF]

				Y. Chen, Y. Tang, M.-T. Wang, S. Zeng, and D. Nie Human Pregnane X Receptor and Resistance to Chemotherapy in Prostate Cancer Cancer Res., November 1, 2007; 67(21): 10361 - 10367. [Abstract] [Full Text] [PDF]

				H. Masuyama, H. Nakatsukasa, N. Takamoto, and Y. Hiramatsu Down-Regulation of Pregnane X Receptor Contributes to Cell Growth Inhibition and Apoptosis by Anticancer Agents in Endometrial Cancer Cells Mol. Pharmacol., October 1, 2007; 72(4): 1045 - 1053. [Abstract] [Full Text] [PDF]

				H. K. Choi, J. W. Yang, S. H. Roh, C. Y. Han, and K. W. Kang Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells Endocr. Relat. Cancer, June 1, 2007; 14(2): 293 - 303. [Abstract] [Full Text] [PDF]

				A. Takeshita, K. Inagaki, J. Igarashi-Migitaka, Y. Ozawa, and N. Koibuchi The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells. J. Endocrinol., September 1, 2006; 190(3): 897 - 902. [Abstract] [Full Text] [PDF]

				Y. Miki, T. Suzuki, K. Kitada, N. Yabuki, R. Shibuya, T. Moriya, T. Ishida, N. Ohuchi, B. Blumberg, and H. Sasano Expression of the Steroid and Xenobiotic Receptor and Its Possible Target Gene, Organic Anion Transporting Polypeptide-A, in Human Breast Carcinoma Cancer Res., January 1, 2006; 66(1): 535 - 542. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]

				J. Orans, D. G. Teotico, and M. R. Redinbo The Nuclear Xenobiotic Receptor Pregnane X Receptor: Recent Insights and New Challenges Mol. Endocrinol., December 1, 2005; 19(12): 2891 - 2900. [Abstract] [Full Text] [PDF]

				H. Masuyama, N. Suwaki, Y. Tateishi, H. Nakatsukasa, T. Segawa, and Y. Hiramatsu The Pregnane X Receptor Regulates Gene Expression in a Ligand- and Promoter- Selective Fashion Mol. Endocrinol., May 1, 2005; 19(5): 1170 - 1180. [Abstract] [Full Text] [PDF]