|Budget Amount *help
¥14,400,000 (Direct Cost : ¥14,400,000)
Fiscal Year 2000 : ¥4,600,000 (Direct Cost : ¥4,600,000)
Fiscal Year 1999 : ¥4,300,000 (Direct Cost : ¥4,300,000)
Fiscal Year 1998 : ¥5,500,000 (Direct Cost : ¥5,500,000)
Clinical observations, that a large number of mast cells containing heparin reside in leiomyoma and that leiomyoma often enlarge rapidly during pregnancy, encouraged us to study the effect of heparin and HCG on the growth of leiomyomal cells. Then, heparin inhibited the proliferation of leiomyomal cells through the induction of α-smooth muscle actin (SMA), calponin h1 and p27. This suggests that heparin from mast cells may induce differentiation in leiomyomal cells and may influence tissue remodeling and reconstruction during tumorgenesis of leiomyoma. In contrast, HCG directly promoted the proliferation of leiomyomal cells and the result was compatible with the clinical observation.
To determine the genetic difference of smooth muscle tumors the uterus, the expression of estrogen receptors (ER), progesterone receptors (PR), tumor suppressor concogene p53, Ki-67, cyclin E, cyclin A, cdk2, cdc2 and calponin h1 was examined in smooth muscle tumors of the uterus. Then, reduced expression
of ER, PR and calponin h1 with increased expression of p53, Ki-67, cyclin E, cyclin A, cdk2, and cdc2 was associated in leiomyosarcomas of the uterus. The vice versa results were obtained in leiomyoma.
Uterine leiomyosarcoma is a rare, but lethal, tumor. The genetic analysis of leiomyosarcoma has revealed that this tumor exhibits a diminished expression of calponin h1, which is normally expressed in smooth muscle cells of healthy myometria and in leiomyoma (a benign tumor of smooth muscle). Transfection of the calponin h1 gene into human leiomyosarcoma cells resulted in morphologic modifications that resembled the appearance of cultured normal myometrial smooth muscle cells. Furthermore, in vivo tumorgenicity was significantly reduced by this treatment. Therefore, calponin h1 is a prospective tumor suppressor for leiomyosarcoma. Clinically, the transfer of calponin h1 cDNA into poorly differentiated leiomyosarcoma cells could have therapeutic potential through induction of a normal, differentiated cellular phenotype. Less