This Article Full Text (PDF) References Alert me when this article is cited 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 Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Chegini, N. Articles by Kornberg, L. Search for Related Content PubMed PubMed Citation Articles by Chegini, N. Articles by Kornberg, L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LEUPROLIDE Medline Plus Health Information Uterine Cancer Uterine Fibroids Social Bookmarking                         What's this?

Gonadotropin Releasing Hormone Analogue Therapy Alters Signal Transduction Pathways Involving Mitogen-Activated Protein and Focal Adhesion Kinases in Leiomyoma

Departments of Obstetrics and Gynecology and Otolaryngology, University of Florida, Gainesville, Florida; Department of OB/GYN, University of Florida, Box 100294, Gainesville, FL 32610 cheginin{at}obgyn.ufl.edu

Lori Kornberg, PhD

Departments of Obstetrics and Gynecology and Otolaryngology, University of Florida, Gainesville, Florida

Objective: Because gonadotropin releasing hormone analogue (GnRHa) therapy often causes leiomyoma regression, in part through alteration of growth factor and receptor expression, we determined whether GnRHa therapy alters the expression of extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK), which are linked to intracellular signaling pathways activated by ovarian steroids, growth factors, and adhesion molecules.

Methods: Leiomyoma and matched unaffected myometrium were collected from women who received GnRHa therapy (n = 5) and untreated women (n = 10). We determined the expression of ERK1, ERK2, FAK, phosphorylated ERK (pERK1/2), and pFAK using Western blotting and immunohistochemical analysis.

Results: Leiomyoma and myometrium expressed ERK1 (44 kD), ERK2 (42 kD), and FAK (125 kD) at variable levels with increased ERK2, pERK, and FAK expression in leiomyoma. We found that GnRHa therapy resulted in a noticeable decrease in ERK2 and FAK, with significant reduction in pERK1/2 and low or undetectable levels of pFAK in both leiomyoma and myometrium compared with the untreated group (P < .05). Immunohistochemically ERK1, ERK2, FAK, pERK1/2, and pFAK were localized in smooth muscle cells and connective tissue fibroblasts in gnRHa-treated and untreated leiomyoma and myometrium, with considerable reduction in their intensity as indicated by HScore in GnRHa-treated tissues.

Conclusion: The data provide further evidence that leiomyoma regression induced by GnRHa is mediated in part through a mechanism involving suppression of signal transduction pathways involving growth factors or ovarian steroid and adhesion molecules.

Key Words: Leiomyoma • gonadotropin releasing hormone analogues • mitogen-activated protein kinase • focal adhesion kinase

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 1, 21-26 (2003)
DOI: 10.1177/107155760301000105


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?