title: Sodium butyrate/retinoic acid costimulation induces apoptosis-independent growth arrest and cell differentiation in normal and ras-transformed seminal vesicle epithelial cells unresponsive to retinoic acid.
abstract: Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-ras-transformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10(-((7( M RA did not produce significant changes in the morphological and biochemical parameters analyzed. When RA was used in combination with 2 mM NaB, the treatment induced substantial morphological changes, apoptosis-independent growth arrest, up-regulation of tissue transglutaminase (tTGase), and down-regulation of beta and gamma RA receptor (RAR) mRNA expression. The same cells did not express RAR alpha either before or after NaB/RA treatment. A similar treatment did not change the amount of mRNA coding for the protein SV-IV (a typical differentiation marker of the SV epithelium) in normal or ras-transformed cells nor the level of v-Ki-ras mRNA in Ki-SVC1 cells. These findings suggest that a defective RA/RARs signaling pathway is probably the biochemical condition that underlies the unresponsiveness to RA of our in vitro culture system, and indirectly points to the possibility that the NaB/RA-induced effects were brought about by a cooperation at the transcription level between the histone deacetylase inhibitory activity of NaB and the ability of RA/RAR to modulate the expression of various genes involved in the control of cell growth and differentiation.
authors.affiliation: CNR International Institute of Genetics and Biophysics, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Buommino
authors.forename: D
authors.initials: D
authors.lastname: Pasquali
authors.forename: A A
authors.initials: AA
authors.lastname: Sinisi
authors.forename: A
authors.initials: A
authors.lastname: Bellastella
authors.forename: F
authors.initials: F
authors.lastname: Morelli
authors.forename: S
authors.initials: S
authors.lastname: Metafora
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002461:Cell Line, Transformed; D017931:DNA Primers; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011905:Genes, ras; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D012669:Seminal Vesicles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D017931:DNA Primers; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D011503:Transglutaminases