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This version published online on December 16, 2004
Endocrinology, doi:10.1210/en.2004-1384
A more recent version of this article appeared on March 1, 2005
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*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Uterine Cancer
*Uterine Fibroids

Submitted on October 20, 2004
Accepted on December 1, 2004

Leiomyoma and Myometrial Gene Expression Profiles and Their Response to Gonadotropin Releasing Hormone Analogue (GnRHa) Therapy

Xiaoping Luo, Li Ding, Jingxia Xu, R. Stan Williams, and Nasser Chegini*

Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida 32610

* To whom correspondence should be addressed. E-mail: cheginin{at}obgyn.ufl.edu.

Gene microarray was used to characterize the molecular environment of leiomyoma and matched myometrium during growth and in response to GnRHa therapy, as well as GnRHa direct action on primary cultures of leiomyoma and myometrial smooth muscle cells (LSMC and MSMC). Unsupervised and supervised analysis of gene expression values and statistical analysis in R programing with a false discovery rate of P ≤ 0.02 resulted in identification of 153 and 122 differentially expressed genes in leiomyoma and myometrium in untreated and GnRHa-treated cohorts, respectively. The expression of 170 and 164 genes was affected by GnRHa therapy in these tissues compared with their respective untreated group. GnRHa (0.1 µM) in a time-dependent manner (2, 6 and 12 h) targeted the expression of 281 genes (P ≤ 0.005) in LSMC and MSMC of which 48 genes were found in common with GnRHa-treated tissues. Functional annotations assigned these genes as key regulators of processes involving transcription, translational, signal transduction, structural activities and apoptosis. We validated the expression of IL-11, EGR3, TGIF, TIEG, CITED2, Nur77, Gas-1, p27, p57 and GRPK5 representing cytokine, common transcription factors, cell cycle regulators, and signal transduction at tissue levels and in LSMC and MSMC in response to GnRHa time-dependent action using Realtime PCR, Western blotting and immunohistochemistry. In conclusion, using different, complementary approaches we characterized leiomyoma and myometrium molecular fingerprints and identified several previously unrecognized genes as targets of GnRHa action, implying that local expression and activation of these genes may represent features differentiating leiomyoma and myometrial environments during growth and GnRHa-induced regression.
Key words: GnRHa • leiomyoma • gene profiling • expression • regulation




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