Expression and potential roles of pregnane X receptor in endometrial cancer

Hisashi Masuyama, Yuji Hiramatsu, Jun Ichi Kodama, Takafumi Kudo

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 ERα.

Original languageEnglish
Pages (from-to)4446-4454
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

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Endometrial Neoplasms
Tissue
Xenobiotics
Estrogen Receptors
Cytochrome P-450 Enzyme System
Endocrine Disruptors
Estrogens
Steroids
Metabolism
Steroid hormones
Gonadal Hormones
Cytochrome P-450 CYP3A
pregnane X receptor
Progesterone Receptors
Cytoplasmic and Nuclear Receptors
Growth and Development
Tumors
Neoplasms
Genes
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Expression and potential roles of pregnane X receptor in endometrial cancer. / Masuyama, Hisashi; Hiramatsu, Yuji; Kodama, Jun Ichi; Kudo, Takafumi.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 9, 01.09.2003, p. 4446-4454.

Research output: Contribution to journalArticle

Masuyama, Hisashi ; Hiramatsu, Yuji ; Kodama, Jun Ichi ; Kudo, Takafumi. / Expression and potential roles of pregnane X receptor in endometrial cancer. In: Journal of Clinical Endocrinology and Metabolism. 2003 ; Vol. 88, No. 9. pp. 4446-4454.
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