Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenylyl Cyclases / metabolism
-
Animals
-
Antineoplastic Agents / pharmacology*
-
Apoptosis / drug effects
-
Cell Division / drug effects
-
Cell Line, Transformed
-
Cell Membrane / drug effects
-
Cell Membrane / metabolism
-
Cyclic AMP / analysis
-
Cytosol / drug effects
-
Cytosol / metabolism
-
Dose-Response Relationship, Drug
-
Down-Regulation
-
Hemangiosarcoma / pathology
-
Neoplasm Transplantation
-
Protein Kinase C / metabolism
-
Proto-Oncogene Proteins p21(ras) / analysis
-
Proto-Oncogene Proteins p21(ras) / genetics
-
Proto-Oncogene Proteins p21(ras) / metabolism*
-
RNA, Messenger / analysis
-
Rats
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction / drug effects
-
Tretinoin / pharmacology*
Substances
-
Antineoplastic Agents
-
RNA, Messenger
-
Tretinoin
-
Cyclic AMP
-
Protein Kinase C
-
Proto-Oncogene Proteins p21(ras)
-
Adenylyl Cyclases