Expression Data from PtenF341V and Null Mouse Embryonic Fibroblasts

PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor mechanisms are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN that differentially alter the Akt axis in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation. These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients

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Caserta E, Egriboz O, Wang H, Martin C, Koivisto C, Pecót T, Kladney RD, Shen C, Shim KS, Pham T, Karikomi MK, Mauntel MJ, Majumder S, Cuitino MC, Tang X, Srivastava A, Yu L, Wallace J, Mo X, Park M, Fernandez SA, Pilarski R, La Perle KM, Rosol TJ, Coppola V, Castrillon DH, Timmers C, Cohn DE, O'Malley DM, Backes F, Suarez AA, Goodfellow P, Chamberlin HM, Macrae ER, Shapiro CL, Ostrowski MC, Leone G