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Expression and Functional Analysis of Pituitary Tumor Transforming Growth Factor-1 in Uterine Leiomyomas

Departments of Physiology (S.-J.T., S.-J.L., L.-Y.C.W.) and Obstetrics and Gynecology (Y.-M.C.) and Institute of Basic Medicine (H.-M.C.), College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

Address all correspondence and requests for reprints to: Dr. Lih-Yuh C. Wing, Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan. E-mail: wing{at}mail.ncku.edu.tw.

Pituitary tumor-transforming gene-1 (PTTG-1) is a novel protooncogene 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 the 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 the 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 up-regulated in human uterine leiomyomas and that the positive feedback loop between PTTG-1 and bFGF may be pivotal in the growth of leiomyoma cells.

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