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This version published online on March 15, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2303
A more recent version of this article appeared on June 1, 2005
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Submitted on November 24, 2004
Accepted on March 4, 2005

Expression and functional analysis of pituitary tumor transforming growth factor-1 in uterine leiomyomas

Shaw-Jenq Tsai, Shu-Jeg Lin, Ya-Ming Cheng, Hsiu-Mei Chen, and Lih-Yuh C. Wing*

Departments of Physiology and Obstetrics and Gynecology, and the Institute of Basic Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

* To whom correspondence should be addressed. E-mail: wing{at}mail.ncku.edu.tw.

Pituitary tumor transforming gene-1 (PTTG-1) is a novel proto-oncogene overexpressed in numerous cancer cell lines and cancers. In this study, we elucidate the expression of PTTG-1 in uterine leiomyomas and its functional role in the development of this disease. By comparing 23 pairs of leiomyomas and matched pairs of myometria, we found that expression of PTTG-1 is significantly elevated in leiomyoma. The expression of PTTG-1 is independent of the menstrual cycle and is not affected by ovarian hormones. In contrast, basic fibroblast growth factor (bFGF) time- and dose-dependently stimulates PTTG-1 expression, which results in increasing cell proliferation. Forced expression of PTTG-1 by transient transfection stimulates bFGF and VEGF expression as well as changes the expression pattern of cell cycle proteins. Western blotting analysis demonstrates that expressions of PTTG-1, bFGF, and the cell proliferation marker, proliferating cell nuclear antigen, are positively correlated with each other, which supports the hypothesis that the positive feedback loop between PTTG-1 and bFGF increases leiomyoma-cell proliferation. In summary, we have shown for the first time that PTTG-1 is upregulated in human uterine leiomyomas and that the positive feedback loop between PTTG-1 and bFGF may be pivotal in the growth of leiomyoma cells.
Key words: bFGF • Leiomyoma • Proliferation • PTTG-1 • Uterus




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