Taken together with the above studies, our results that knockdown of AMPK subunits did not rescue the inhibitory effects of metformin on mTOR/p70S6K phosphorylation but that mTOR reexpression was able to reverse the anti-proliferative effects of metformin, suggest that the activation of AMPK and inhibition of the mTOR/p70S6K pathway by metformin are independent events that may both contribute to cancer cell growth inhibition. The gene discussed is PRKAA1; the disease is cancer.