Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

作者：Ng Stanley K L; Neo Soek Ying^*; Yap Yann Wan; Karuturi R Krishna Murthy; Loh Evelyn S L; Liau Kui Hin; Ren Ee Chee

来源：Biochemical and Biophysical Research Communications, 2009, 387(2): 310-315.

DOI：10.1016/j.bbrc.2009.07.013

• HCC
• Phosphoinositide-3-kinase
• PI3K
• Cell growth
• Liver
• Apoptosis
• PIK3C2 alpha

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 (PIK3C2 alpha) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2 alpha mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2 alpha 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 PIK3C2 alpha can modulate HCC cell growth.

• 出版日期2009-9-18