Conditional abrogation of Transforming Growth Factor Beta Receptor 1 in PTEN ‐inactivated endometrium promotes endometrial cancer progression in mice

ABSTRACT Although a putative role for TGF beta (TGFB) signaling in the pathogenesis of human endometrial cancer has long been proposed, the precise function of TGFB signaling in the development and progression of endometrial cancer remains elusive. Depletion of PTEN in the mouse uterus causes endometrial cancer. To identify the potential role of TGFB signaling in endometrial cancer, we simultaneously deleted TGFB receptor 1 (Tgfbr1) and Pten in the mouse uterus using Cre‐recombinase driven by the progesterone receptor (termed Ptend/d; Tgfbr1d/d). We found that Ptend/d; Tgfbr1d/d mice developed severe endometrial lesions that progressed more rapidly compared with those resulting from conditional deletion of Pten alone, suggesting that TGFB signaling synergizes with PTEN to suppress endome...

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