SM22alpha inhibits cell proliferation and protects against anticancer drugs and gamma-radiation in HepG2 cells: involvement of metallothioneins.
Smooth muscle protein 22-alpha (SM22alpha) has been postulated to affect the structure and function of the actin filament. In this study, we report on the significant induction of SM22alpha by cytotoxic agents in HepG2 cells. SM22alpha-overexpression inhibited the activation of IGF-1Rbeta/Akt and Erk, consequently suppressing cell proliferation. On the other hand, SM22alpha-overexpressing cells became resistant to apoptotic cell death caused by cytotoxic agents, in which metallothionein (MT) isoforms, especially MT1G, were significantly induced. MT1G-overexpression also conferred cellular resistance, and SM22alpha regulated the expression of MT1G at a transcriptional level. This study provides the first demonstration of SM22alpha-induced blockage of cell proliferation and cellular resistance to overcome the detrimental effects of damaging agents.
Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejeon 305-600, Republic of Korea.
Tae Rim
TR
Kim
Ji Hye
JH
Moon
Hee Min
HM
Lee
Eun Wie
EW
Cho
Sang Gi
SG
Paik
In Gyu
IG
Kim
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D005786:Gene Expression Regulation; D006801:Humans; D047311:Luteolin / Q000494:pharmacology; D008668:Metallothionein / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D008840:Microfilament Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C051615:transgelin; D008668:Metallothionein; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D047311:Luteolin