The Differential expression of matrix metalloproteinase and their tissue inhibitors in myometrium and leiomyoma

Yoo, Eun Hee; Whang, Eun Mi; Yu, Han Ki; Kim, Seung Bo

Abstract

OBJECTIVES
To determine the level of mRNA expression of various members of the matrix metalloproteinase and tissue inhibitors in uterine leiomyoma compared with unaffected myometrium. Materials & Method: 30 cases of portions of leiomyoma and myometrium were collected immediately followimg hysterectomy. Thirteen cases were from proliferative phase and seventeen were from secretory phase of menstrual cycle. The mean age was 43.7years old. The level of expression of mRNAs of interstitial collagenase, gelatinase, stromelysin, TIMP-1,-2,-3 was determined by reverse transcriptase-polymerase chain reaction(RT-PCR) and normalized to GAPDH(glyceraldehyde-3-phosphate dehydrogenase) mRNA.
RESULTS
Myometrium and leiomyoma expressed all the members of above mentioned matrix metalloproteinase family and tissue inhibitors. Leiomyoma expressed a significantly higher level of stromelysin-3 during secretory phase, an extremely lower level of 92kDa gelatinase and a significantly lower level of TIMP-3. The immunohistochemical localization of TIMP-3 was smooth muscle cell and arteriole wall of myometrium and leiomyoma.
CONCLUSIONS
The increased expression of stromelysin-3 in uterine leiomyoma compared with myometrium suggests that this MMP may be involved in the formation of a more fibrous extracellular matrix in leiomyoma. The extremely lower expression of 92kDa gelatinase of leiomyoma means that leiomyoma do not invade myometrium and forms a separated mass. Decreased expression of TIMP-3 of leiomyoma suggests that TIMP-3 is required for differentiation and homeostasis of extracellular matrix of normal myometrium and function as a suppressive role of tumor development