mTOR Signaling Pathway Components in Colorectal Cancer (original) (raw)

2010, Journal of the American College of Surgeons

BACKGROUND-The PI3K/Akt/mTOR pathway plays a critical role in the growth and progression of colorectal cancer (CRC). The purpose of our study was twofold: 1) to determine the expression levels of several key components of this pathway including p85α, Akt1, Akt2, p-mTOR Ser2448 and p-p70S6K Thr389 in CRCs, and 2) to correlate the expression of these proteins with cancer stage and location (left-vs. right-sided). STUDY DESIGN-Immunohistochemistry for p85α, Akt1, Akt2, p-mTOR Ser2448 and p-p70S6K Thr389 was performed on normal colon and CRCs from 154 patients. RESULTS-All proteins investigated were significantly overexpressed in CRCs compared to matched normal colonic tissue from the same patient (p<0.0001). The PI3K pathway component proteins were moderately correlated across normal and malignant colon tissues; correlations tended to be stronger in normal tissues as compared to the same correlations in cancers. Expression levels of p85α were significantly higher in Stage IV cancers than in Stage I-III cancers (p = 0.0005); interestingly, p85α expression was also significantly increased in the adjacent normal colonic mucosa of patients with Stage IV CRC compared with earlier stages (p=0.003). Finally, expression of Akt1, Akt2, and p-p70S6K Thr389 was higher in left-sided CRCs compared with CRCs in the right colon (p = 0.007, p = 0.0008, and p = 0.04, respectively). CONCLUSIONS-The PI3K/Akt/mTOR pathway components, p85α, Akt1, Akt2, p-mTOR Ser2448 and p-p70S6K Thr389 , are highly overexpressed in CRCs thus providing the rationale