A Deregulated PI3K-AKT Signaling Pathway in Patients with Colorectal Cancer

Molecular switches in phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway may serve as potential targets for the treatment of colorectal cancer (CRC). This study aims to profile the gene alterations involved in PI3K-AKT signaling pathway in patients with CRC.

Tumoral and matched peritumoral tissues were collected from 15 CRC patients who went routine surgery. A human PI3K-AKT signaling pathway polymerase chain reaction (PCR) array, which profiled the transcriptional changes of a total number of 84 genes involved in the PI3K-AKT pathway, was then applied to determine the gene alterations in CRC tumoral tissue with matched peritumoral tissue as a healthy control. Subsequent real-time reverse transcription PCR and western blot (WB) with different subgroups of CRC patients were then performed to further validate the array findings.

The PCR array identified 14 aberrantly expressed genes involved in the PI3K-AKT signaling pathway in CRC tumoral tissue, among which 12 genes, CCND1, CSNK2A1, EIF4E, EIF4EBP1, EIF4G1, FOS, GRB10, GSK3B, ILK, PTK2, PTPN11, and PHEB were significantly up-modulated (> two fold) while the remaining two, PDK1 and PIK3CG, were down-regulated (> two fold). These genes involve in the regulation of gene transcription and translation, cell cycle, and cell growth, proliferation, and differentiation. The real-time reverse transcription PCR validation agreed with the array data towards the tested genes, CCND1, EIF4E, FOS, and PIK3CG, while it failed to obtain similar result for PDK1. Interestingly, the WB analyses were further consistent with the PCR results that the protein levels of CCND1, EIF4E, and FOS were apparently up-regulated and that protein PIK3CG was down-modulated.

Taken together, the present study identified a deregulated PI3K-AKT signaling pathway in CRC patients, which might serve as therapeutic target(s).