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Expression of Proliferative and Preapoptotic Molecules in Human Myometrium and Leiomyoma Throughout the Menstrual Cycle

Murat Berkkanoglu, MD

Gulnur Kizilay, PhD

Levent Senturk, MD

Aydin Arici, MD

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, & Reproductive Sciences,Yale University School of Medicine, New Haven, CT, aydin.arici{at}yale.edu

The pathogenesis of leiomyoma may be related to an imbalance in the interaction of sex steroids with paracrine growth factors that may control the modulation of mitogenesis and local immunity. The authors investigate the temporal and spatial expression of proliferative and preapoptotic molecules that may participate in the modulation of myometrial function and leiomyoma pathogenesis. Immunohistochemistry and Western blot analysis are used to investigate Fas ligand (FasL), phosphatase and tensin homolog deletion on chromosome 10 (PTEN), and proliferating cell nuclear antigen (PCNA) expression in myometrium and leiomyoma. Western blot results show that in the secretory phase, FasL expression is 1.8-fold and 2.3-fold higher compared with the proliferative phase in the myometrium and leiomyoma, respectively (P = .022 and .047, respectively). A paired comparison between myometrium and leiomyoma reveals higher FasL expression in the leiomyoma (P = .003). On the contrary, when compared with the secretory phase, PCNA expression during the proliferative phase is 4.6-fold and 3.7-fold higher in the myometrium and leiomyoma, respectively (P = .041 and .034, respectively). A paired comparison between myometrium and leiomyoma reveals higher PCNA expression in the leiomyoma. Furthermore, lower PTEN expression is detected in the leiomyoma compared with the myometrium (P < .032). Immunohistochemistry results reveal that FasL, PTEN, and PCNA are expressed in the myometrium and leiomyoma, consistent with the results from the Western blot analysis. The results suggest that FasL, PTEN, and PCNA may be involved in the pathophysiology of leiomyoma. A higher FasL level in the leiomyoma is likely to correspond to suppression of local immunity by inducing apoptosis of immune cells, while a higher level of PCNA and a lower level of PTEN may be related to increased mitogenesis and decreased apoptosis in leiomyoma.

Key Words: Fas ligand • PTEN ,PCNA • leiomyoma • myometrium.

Reproductive Sciences, Vol. 14, No. 7, 678-686 (2007)
DOI: 10.1177/1933719107305866


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