Estrogenic and antiestrogenic regulation of MMP-2 and MMP-13 mRNA in RUCA-I endometrial tumor cells in vitro and in vivo.
We investigated the influence of estrogenic and antiestrogenic treatment on proteolytic activity--especially on MMP-2 and MMP-13--in the RUCA-I transplantable endometrial tumor model. Morphological studies demonstrate that RUCA-I cells are forming highly differentiated gland-like structures by remodelling and invading the underlying ECM. Estrogens upregulate the mRNA levels of MMP-2 and MMP-13 in the rat uterus. Treatment with the pure antiestrogen ICI 182,780 results in the downregulation of MMP-2 and MMP-13 mRNA. The same regulation for MMP-13 mRNA is found in vitro in RUCA-I cells. In contrast, in the transplantation tumor, the mRNA level of MMP-13 is repressed by estrogens and induced by ICI 182,780. MMP-2 mRNA is not regulated by hormones in the transplantation tumor and in RUCA-I cells. The divergent regulation suggests a varying influence of cell-cell-, cell-extracellular matrix interactions and soluble factors.
Tüshaus
Ludger
L
Institut für Molekulare Medizin, Universität zu Lübeck, 23538 Lübeck, Germany.
Hopert
Anne-Christine
AC
Strunck
Elisabeth
E
Schubert
Christine
C
Wünsche
Winfried
W
Vollmer
Günter
G
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D017364:Collagenases / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D020778:Matrix Metalloproteinase 2