Repression of SV40 T oncoprotein expression by DMSO.
SV40 large T oncoprotein-transformed murine mesenchymal 3T3 T stem cells (CSV3 cells) can be induced to growth arrest and then differentiate into adipocytes. When differentiation occurs, SV40 T oncoprotein expression is repressed (Estervig et al., J Virol 63:2718, 1989). To determine if repression of T oncoprotein expression can also be induced pharmacologically, the effect of a variety of agents that have been reported to effect differentiation in various cell types but not in 3T3 T or CSV3 cells was tested. This rationale suggests that if any of these agents repress T oncoprotein expression in CSV3 cells, then the results would establish that repression of T oncoprotein expression can be mediated by mechanisms independent of overt differentiation. The results show that dimethylsulfoxide (DMSO) is the only agent tested that represses T oncoprotein expression in CSV3 cells. Repression occurs in a dosage-dependent manner within 24-96 hours after exposure to DMSO. The effect of DMSO on T oncoprotein expression is mediated by posttranslational mechanisms that decrease the stability of the T oncoprotein. DMSO-induced repression of T oncoprotein expression is also associated with reversion of the transformed phenotype in CSV3 cells as demonstrated by the loss of responsiveness to a specific transformation-associated mitogen. These data support the conclusion that the pharmacological repression of T oncoprotein expression represents a form of cancer suppressor activity that can be mediated by a distinct molecular mechanism.
Department of Pathology, University of Tennessee Medical Center, Memphis 38163.
M M
MM
Witte
R F
RF
Parker
H
H
Wang
R E
RE
Scott
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D000081:Acetamides; D000952:Antigens, Polyomavirus Transforming; D002087:Butyrates; D007328:Insulin; D020148:Butyric Acid; D014212:Tretinoin; D007372:Interferons; C014026:hexamethylene bisacetamide; D001374:Azacitidine; D004121:Dimethyl Sulfoxide