Document Detail

The association of transforming growth factor-beta 1 with myometrial invasion of endometrial carcinomas through effects on matrix metalloproteinase.
MedLine Citation:
PMID:  10932976     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.
H Yabushita; H Narumiya; K Hiratake; H Yamada; M Shimazu; K Sawaguchi; M Noguchi; M Nakanishi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The journal of obstetrics and gynaecology research     Volume:  26     ISSN:  1341-8076     ISO Abbreviation:  J. Obstet. Gynaecol. Res.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-08-17     Completed Date:  2000-08-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9612761     Medline TA:  J Obstet Gynaecol Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  163-70     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Aichi Medical University, Japan.
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MeSH Terms
Adenocarcinoma / chemistry,  enzymology,  pathology*
Colonic Neoplasms / chemistry,  pathology
Endometrial Neoplasms / chemistry,  enzymology,  pathology*
Gelatinases / metabolism
Matrix Metalloproteinase 9 / analysis
Matrix Metalloproteinases / metabolism*
Myometrium / pathology*
Neoplasm Invasiveness*
Neoplasm Staging
Receptors, Transforming Growth Factor beta / analysis
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Transforming Growth Factor beta / analysis,  blood*,  pharmacology
Tumor Cells, Cultured
Reg. No./Substance:
0/Receptors, Transforming Growth Factor beta; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Transforming Growth Factor beta; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 9

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