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- W2318385364 abstract "The precise molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been clearly delineated. Here, we report that defects in the TGF-β and PI3K/Akt signaling pathways are common in human HNSCCs. Activation of the PI3K/Akt pathway due to PTEN deletion gives rise to hyperproliferation in the head and neck epithelia, but only a few lesions progressed to HNSCCs. Strikingly, PTEN deletion, in combination with a loss of Tgfbr1, caused HNSCC with complete penetrance. Molecular analysis revealed enhanced cell proliferation, increased expression of CCND1 and decreased expression of CDKN1A in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/PTEN double conditional knockout (2cKO) mice. These tumors displayed pathology and multiple molecular alterations that resembled human HNSCCs. Furthermore, the neoplastic transformation was due to senescence evasion and was associated with an increased number of putative (CD44+, CD133+) cancer stem cells. In addition, myeloid derived suppressor cell (MDSC) infiltration, angiogenesis and immune suppression in the tumor microenvironment also accompanied mouse head and neck carcinogenesis. The Tgfbr1/PTEN 2cKO mouse model is suitable for preclinical intervention and has significant implications in the development of diagnostic cancer biomarkers as well as effective preventive and therapeutic strategies for the treatment of HNSCCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4324. doi:10.1158/1538-7445.AM2011-4324" @default.
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- W2318385364 date "2011-04-15" @default.
- W2318385364 modified "2023-09-27" @default.
- W2318385364 title "Abstract 4324: Loss of TGF-beta receptor I and PTEN promotes HNSCC" @default.
- W2318385364 doi "https://doi.org/10.1158/1538-7445.am2011-4324" @default.
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