ALPK2 is Crucial for Luminal Apoptosis and DNA Repair-related Gene Expression in a Three-dimensional Colonic-crypt Model

作者：Yoshida Yasuhiro; Tsunoda Toshiyuki; Doi Keiko; Fujimoto Takahiro; Tanaka Yoko; Ota Takeharu; Ogawa Masahiro; Matsuzaki Hiroshi; Kuroki Masahide; Iwasaki Akinori; Shirasawa Senji^*

来源：Anticancer Research, 2012, 32(6): 2301-2308.

• ALPK2
• three-dimensional culture
• colorectal cancer
• apoptosis
• DNA repair-related genes

Background: Oncogenic KRAS signaling is dysregulated in a three-dimensional (3D)-specific manner in human colorectal cancer (CRC) HCT116 cells. However, the identity of the crucial genes which are down-regulated through oncogenic KRAS in 3D cultures remains unclear. Materials and Methods: We established a specific anti-alpha-kinase 2 (ALPK2) antibody and addressed the ALPK2 function in HKe3 cells, which are HCT116 cells with a disruption in oncogenic KRAS, in a 3D colonic-crypt model. Results: In HKe3 cells grown in 3D culture, ALPK2 siRNA inhibited luminal apoptosis and reduced the expression of cleaved caspase-3. Furthermore, ALPK2 siRNA reduced the expression of DNA repair genes. Reduced expression of ALPK2 mRNA was found to be correlated with clinical colorectal adenomas in a public dataset of gene expression analyses. Conclusion: ALPK2, down-regulated by oncogenic KRAS, is crucial for laminal apoptosis and expression of DNA repair-related genes, possibly in the transition of normal colonic crypt to adenoma.

• 出版日期2012-6