Treatment of v-Ki-ras-transformed SVC1 cells with low retinoic acid induces malignancy reversion associated with ras p21 down-regulation.
The effect of nontoxic, low concentrations (10(-8) M) of retinoic acid (RA) for a relatively long time (28 days) on a Kirsten ras-virus transformed cell line (Ki-SVC1), derived from the rat seminal vesicle epithelium, was investigated. In these experimental conditions, the cell treatment with RA induced a decrease of the proliferation rate, apoptosis and a marked reduction of both anchorage-independent growth and tumorigenicity. These biological responses were either preceded or associated with important changes in adenylate cyclase/protein kinase C signaling pathways, the activation of important apoptosis-linked genes and a marked decrease of the v-Ki-ras p21 protein. The significance of these findings is discussed.
Spina
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Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy.
Chiosi
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Naviglio
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Pagano
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Illiano
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Marchese
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Spena
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Buommino
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Morelli
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Metafora
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006394:Hemangiosarcoma / Q000473:pathology; D009368:Neoplasm Transplantation; D011493:Protein Kinase C / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D014212:Tretinoin; D000242:Cyclic AMP; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras); D000262:Adenylyl Cyclases