[Retinoic acid-induced cell growth inhibition and differentiation in testicular carcinoma cells in culture].
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.
Ueno
M
M
Department of Urology, Saitama Medical School, Japan.
Nakashima
J
J
Nakanoma
T
T
Ohigashi
T
T
Hirata
R
R
Iida
M
M
Suzuki
M
M
Sano
M
M
Yamada
Y
Y
Deguchi
N
N
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018237:Germinoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D018168:Receptors, Retinoic Acid / Q000819:agonists; D000072482:Retinoic Acid Receptor alpha; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D000509:alpha-Fetoproteins / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007797:Laminin; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins; D014212:Tretinoin