Growth inhibition of SV40-transformed human keratinocytes by TGF-beta s is not linked to dephosphorylation of the Rb gene product.
We found that transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2 inhibited the growth of normal human keratinocytes and their SV40-transformed counterpart in a dose dependent manner. Both normal and SV-40 transformed keratinocytes accumulated in G1 when treated with TGF-beta s. The hyperphosphorylated form of Rb gene product (RB) was reduced by TGF-beta s in normal keratinocytes. In contrast, phosphorylation of RB was not essentially affected in SV-40 transformed cells. This uncoupling of growth kinetics and phosphorylation states of RB in SV-40 transformed keratinocytes suggests that RB is not the primary target of action for TGF-beta s and that additional factors or pathways may be involved in mechanisms of the growth inhibition.
Koike
M
M
Department of Cancer Cell Research, University of Tokyo, Japan.
Ishino
K
K
Huh
N
N
Kuroki
T
T
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016161:Genes, Retinoblastoma; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000302:isolation & purification / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D004247:DNA