Retinoic acid-induced cell growth inhibition and differentiation in testicular carcinoma cells in culture
Ueno, M.; Nakashima, J.; Nakanoma, T.; Ohigashi, T.; Hirata, R.; Iida, M.; Suzuki, M.; Sano, M.; Yamada, Y.; Deguchi, N.
Human Cell 10(3): 151-158
1997
ISSN/ISBN: 0914-7470 PMID: 9436034 Document Number: 474190
Testicular germ tumor cells could be differentiated spontaneously or by some chemotherapeutic compounds. However, the mechanism by which the cells are differentiating from the stem cell remains unclear. The KU-MT cells, which were newly established from lung metastasis of testicular carcinoma, have been continuously producing alpha fetoprotein (AFP). Retinoic acids are well-known to induce cellular differentiation in culture and have already been applied for a clinical usage against leukemia. In the present study, all-trans-retionic acid (ATRA) elevated the level of AFP and inhibited the growth of KU-MT cells in vitro. ATRA also arrested the cell cycle in G1 and reduced the percentage of the S phase cell in terms of wild type p53, leading to apoptosis in part. Retinoids, especially retinoic acid receptor (RAR)-alpha specific agonists induced laminin production, a marker of endodermal differentiation; whereas arotinoid, a retinoid not bound to RAR-alpha, did not affect laminin expression. In summary, retinoic acids could mediate cell growth and differentiation of testicular tumor through RAR-alpha.