KIMURA Tadashi Osaka Univ.Med School Dept.of Obstet.and Gyne.Research Fellow, 医学部, 助手 (90240845)
OHASHI Kazutomo Osaka Univ.Med School Dept.of Obstet.and Gyne.Research Fellow, 医学部, 助手 (30203897)
MATSUZAKI Noboru Osaka Univ.Med School Dept.of Obstet.and Gyne.Instructor, 医学部, 助手 (30199781)
AZUMA Chihiro Osaka Univ.Med School Dept.of Obstet.and Gyne.Instructor, 医学部, 助手 (20151061)
SAJI Fumitaka Osaka Univ.Med School Dept.of Obstet.and Gyne.Assist Professor, 医学部, 講師 (90093418)
|Budget Amount *help
¥6,700,000 (Direct Cost : ¥6,700,000)
Fiscal Year 1993 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1992 : ¥4,300,000 (Direct Cost : ¥4,300,000)
Background. The protease activity leading to degradation of the extracellular matrix was compared between human endometrial and ovarien cancer and normal tissue.
Methods. Conditioned medium from tumor cells and nomal cells was subjected to electrophoresis on sodium dodecyl sulfate(SDS)-polyacrylamide gel containing gelatin as a substrate. After electrophoresis, the gel was stained with Coomassie blue, and then the enzume activity, expressed as the zone of dye clearing, was analyzed by densitomery. The expression of TIMPmRNA was examined by Northern blot analysis.
Results. Densitometric analysis showed that all the endometrial cancers expressed a very high molecular weight enzume activity (Mr 220,000), which was not detected in medium from normal endometrial cells. The analysis also showed that in endometrial cancer the activity of a Mr 92,000 enzyme was always superior to that of a Mr 64,000 enzyme, which was in contrast to the situation for normal encometrium. In ovarian cancer, the activity of a 92KDa gelatinase/type IV collagenase in contrast to the situation in the noomal ovary. Northern blot analysis revealed no remarkable difference of TIMPmRNA expression between cancer and normal ovarian tissues.
Conclusions. These results indicate that the expression of Mr 220,000 enzume activity and the higher activity of the Mr92,000 enzume than the Mr64,000 enzyme are involved in the malignant phenotype of native endometrial cancer. In ovarian cancer, the higher activity of the 92KDa gelatinase / typeIV collagenase enzume, relative to that of the 64KDa enzyme, is involved in the malignant phenotype of ovarian cancer ; while the inhibitor of these enzymes, TIMP, is distributed in a widespread fashion in the tissue, and its levels are not correlated with the malignancy.