| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 20, 2004
Accepted on December 1, 2004
Departments of Obstetrics and Gynecology University of Florida, College of Medicine, Gainesville, Florida 32610
* To whom correspondence should be addressed. E-mail: cheginin{at}obgyn.ufl.edu.
Altered expression of transforming growth factor 
(TGF-) system is recognized to play a central role in various fibrotic disorders including leiomyoma. Here we performed microarray analysis to characterize the gene expression profile of leiomyoma and matched myometrial smooth muscle cells (LSMC and MSMC) in response to the time-dependent action of TGF-, and following pretreatment with TGF- type II receptor (TGF-RII) antisense oligomer blocking/reducing TGF- autocrine/paracrine actions. Unsupervised and supervised assessments of the gene expression values with false discovery rate selected at P 
0.001 identified 310 genes as differentially expressed and regulated in LSMC and MSMC in cell- and time-dependent manners by TGF-. Pretreatment with TGF-RII antisense resulted in changes in the expression of many of the 310 genes regulated by TGF-, with 54 genes displaying a response to TGF- treatment. Comparative analysis of gene expression profile in TGF-RII antisense-treated with GnRHa-treated cells indicated that these treatments target the expression 222 genes in cell specific manner. Gene ontology functionally assigned these genes as cell cycle regulator, transcription factors, signal transduction, tissue turnover and apoptosis. We validated the expression and TGF- time-dependent regulation of IL-11, TGIF, TIEG, EGR3, CITED2, Nur77, RUNX1, RUNX2, p27, p57, Gas-1 and GPRK5 in LSMC and MSMC using Realtime PCR. Together the results provide the first comprehensive assessment of LSMC and MSMC molecular environment targeted by autocrine/paracrine action of TGF-, highlighting potential involvement of specific genes whose products may influence the outcome of leiomyoma growth and fibrotic characteristic by regulating inflammatory response, cell growth, apoptosis, and tissue remodeling.
•
gene expression •
regulation
This article has been cited by other articles:
 |
|
 |
|
  N. J. Laping, J. I. Everitt, K. S. Frazier, M. Burgert, M. J. Portis, C. Cadacio, L. I. Gold, and C. L. Walker Tumor-Specific Efficacy of Transforming Growth Factor-{beta}RI Inhibition in Eker Rats Clin. Cancer Res., May 15, 2007; 13(10): 3087 - 3099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, Y. Wen, M. L. Polan, J. Qiao, and B. H. Chen Increased expression of latent TGF-{beta} binding protein-1 and fibrillin-1 in human uterine leiomyomata Mol. Hum. Reprod., May 1, 2007; 13(5): 343 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-J. Leroy, E. Dallot, I. Czerkiewicz, T. Schmitz, and M. Breuiller-Fouche Inflammation of Choriodecidua Induces Tumor Necrosis Factor Alpha-Mediated Apoptosis of Human Myometrial Cells Biol Reprod, May 1, 2007; 76(5): 769 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Chou and Y.-C. Yang Post-transcriptional Control of Cited2 by Transforming Growth Factor beta: REGULATION VIA SMADS AND CITED2 CODING REGION J. Biol. Chem., July 7, 2006; 281(27): 18451 - 18462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Luo, E. Levens, R. S. Williams, and N. Chegini The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta Hum. Reprod., June 1, 2006; 21(6): 1380 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers In vitro culture significantly alters gene expression profiles and reduces differences between myometrial and fibroid smooth muscle cells Mol. Hum. Reprod., March 1, 2006; 12(3): 187 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Levens, X. Luo, L. Ding, R. S. Williams, and N. Chegini Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling Mol. Hum. Reprod., July 1, 2005; 11(7): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Walker and E. A. Stewart Uterine Fibroids: The Elephant in the Room Science, June 10, 2005; 308(5728): 1589 - 1592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Luo, L. Ding, J. Xu, R. S. Williams, and N. Chegini Leiomyoma and Myometrial Gene Expression Profiles and Their Responses to Gonadotropin-Releasing Hormone Analog Therapy Endocrinology, March 1, 2005; 146(3): 1074 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Levens, X. Luo, L. Ding, R. S. Williams, and N. Chegini Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-{beta} through Smad and MAPK-mediated signalling Mol. Hum. Reprod., July 1, 2005; 11(7): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
