Inhibition of retinoblastoma protein translation by UVB in human melanocytic cells and reduced cell cycle arrest following repeated irradiation.
In human melanocytes and a human melanoma cell line (MM96L), the level of the retinoblastoma gene product (pRB) detected by Western blotting transiently decreased to 55% and 70% of controls respectively 9-12 h after a noncytostatic exposure (75 Jm-2) to UVB (280-315 nm) and to 2% and 14% 48 h after a cytostatic exposure (300 Jm-2). The pRB levels in fibroblasts and HeLa showed minimal loss, and under some conditions increased compared with unirradiated cells. Equitoxic doses of gamma radiation, cisplatin or the antimetabolite deoxyinosine had little effect on pRB levels. UVC (254 nm) was less inhibitory compared with equitoxic UVB. No loss of pRB mRNA was found in MM96L after UVB, nor was pRB protein stability significantly affected. Synthesis of new pRB in MM96L 24 h after UVB was 16% of controls, suggesting that loss of pRB results from a UVB-specific inhibition of translation. Compared with HeLa cells and fibroblasts, MM96L cells exhibited reduced cycle arrest if irradiated when pRB was depleted by a previous UVB exposure. These results suggest a mechanism whereby down-regulation of pRB translation by UVB may play a role in genesis of melanoma.
Pedley
J
J
Queensland Cancer Fund Laboratories, Queensland Institute of Medical Research, Herston, Australia.
Ablett
E M
EM
Pettit
A
A
Meyer
J
J
Dunn
I S
IS
Sturm
R A
RA
Parsons
P G
PG
D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D004355:Drug Stability; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D014176:Protein Biosynthesis / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014466:Ultraviolet Rays
D012333:RNA, Messenger; D016160:Retinoblastoma Protein