|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1997 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Glycoconjugates expressed on cancer cells are involved in the metastases. We have previously reported that endornetrial cancer expressed predominantly Lewis^b antigen, one of the type I carbohydrate chain. Furthermore, our clinicostatiscal study has revealed that endometrial cancer with little expression of Lewis^b showed a low 5 years survival rate, prognosis, beta 1,3-galactosyltransferase (beta 1,3-GT) is involved in the synthesis of type 1 chain, and beta 1,4-galactosyltransferase (beta 1,4-GT) is involved in the synthesis of type 2 chain, respectively. In order to elucidate the biological significance of the type 1 chain and type 2 in endometrial cancer, we transfected human beta 1,4-GT cDNA (beta 1,4-GT cDNA inserted expression vector pCAGGS) into endometrial cancer cell line, SNG-M and studied the biological function between transfectants and SNG-M.Five transfectants with greater expression of beta 1,4-GT mRNA and proteins showed greater adhesiveness to laminin and greater invas
ion abiligy to matrigel compaired to vector control cells. Expression of type 2 glycolipid Le^X of transfectant was higher than that of vector control cells. It is suggested that endometrial cancer cell with increased expression of beta 1,4-GT could have different biological function compared with parental cell line.
Furthermore, we have developed a new procedure for the selective determination of beta 1-3 and beta 1-4 galactosyltransferases. The method was then used to determine the activities of both enzymes in human gynecological carcinoma-derived cells. Four of the five cell lines derived from uterine endometrial cancer expressed significantly high levels of specific activity of beta 1-3GT among the cell lines examined, while their beta 1-4GT activities were less than 20% of that for beta 1-3GT in the endometrial carcinoma-derived cells. On the other hand, a higher specific activity of beta 1-4GT than that of beta 1-3GT was detected in the cell lines derived from uterine cervical and ovarian cancers. These findings were thus found to correlated closely with the rate of expression of Lc_4Cer- and nLc_4Cer-based carbohydrate chains in the cell lines based on the results of immunohistochemical staining. Less