TSC2 and breast cancer: Lastly, in support of the above observations, depletion of tuberin expression by a short-hairpin RNA transduced into breast cancer cells with wild-type TSC2, MCF7, revealed a significant change in the expression of the lung metastasis signature (P = 0.002); thus, genes that when up-regulated mediate lung metastasis showed a trend to be up-regulated with tuberin depletion, and the opposite trend was observed for the down-regulated set (Fig 1F).