title: Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells.
abstract: The human matrix metalloproteinase (MMP)-26, also called matrilysin-2 or endometase, has been isolated as a matrilysin (MMP-7) homolog. Several reports describe that MMP-26 may be related to the development of endometrial carcinomas. Total RNAs were isolated from 51 normal endometrial tissue samples, 6 endometrial hyperplasia tissue samples and 30 endometrial carcinomas. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate MMP-26 mRNA expression levels. We examined the effect of estrogen and its receptor (ER) on MMP-26 expression in endometrial carcinoma cell lines by real-time RT-PCR, western blot analysis and luciferase assays. To examine protein-DNA binding between ER and MMP-26 promoter, we performed chromatin immunoprecipitation (ChIP) assay. Real-time RT-PCR analysis revealed that MMP-26 mRNA expression was significantly higher in the normal human endometria and hyperplasias compared with that in endometrial carcinomas. Estrogen not only transactivated the MMP-26 promoter activity but also enhanced endogenous MMP-26 expression. The MMP-26 promoter region contains a putative ER response element (ERE). Nuclear ER protein interacted with ERE on the MMP-26 promoter by ChIP assay. We found a significant difference in MMP-26 expression in normal and malignant endometrial tissue samples and that estrogen induced MMP-26 expression. Estrogen may induce endometrial hyperplasia but not endometrial carcinoma. Our results provide evidence that regulation of MMP-26 promoter activity by estrogen may represent a mechanism for endometrial carcinogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan. nishih@tokyo-med.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nishi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Isaka
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements; D015533:Transcriptional Activation
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C410599:MMP26 protein, human; D053505:Matrix Metalloproteinases, Secreted