Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation.
Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2alpha) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2alpha mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2alpha was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2alpha can modulate HCC cell growth.
Ng
Stanley K L
SK
Singapore Immunology Network A *STAR, Singapore.
Neo
Soek-Ying
SY
Yap
Yann-Wan
YW
Karuturi
R Krishna Murthy
RK
Loh
Evelyn S L
ES
Liau
Kui-Hin
KH
Ren
Ee-Chee
EC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D058541:Class II Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D058541:Class II Phosphatidylinositol 3-Kinases; D053148:Caspase 3