Abstract LB-129: Evidence from expression profiling, proteomics, metabolomics and FDG-PET of an estrogen-dependent metabolic switch in tuberin-null cells (original) (raw)

Cancer Research, 2013

Abstract

Lymphangioleiomyomatosis (LAM) is a female predominant lung disease characterized by widely-distributed nodules of ‘LAM’ cells and progressive cyst formation that leads to respiratory failure. LAM cells typically have mutation or inactivation of TSC2, leading to mTORC1 activation. We previously demonstrated that estrogen promotes the survival of tuberin-deficient ELT3 cells both in vitro and in vivo, and that estrogen treatment of mice bearing ELT3 cells xenograft tumors promotes lung metastasis. This estrogen-induced cell survival and metastasis was inhibited in vivo by the MEK inhibitor CI-1040. To elucidate pro-survival events mediated by estrogen in tuberin-null cells, we compared Tsc2-null ELT3 cell xenograft tumors from estrogen or placebo-treated mice using expression profiling and proteomic analysis . Expression profiling of ELT3 cell xenograft tumors revealed that estrogen upregulates the expression of genes in lipid and amino acid metabolism pathways. Among these genes, th...

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