Abstract 5777: Translation of HPV mediated immortalization to cancer precision medicine

作者：Aleksandra Dakic, Nancy Palechor-Ceron, Ewa Krawczyk, Hang Yuan, Frank A. Suprynowicz, Seema Agarwal, Richard Schlegel, Vera Simić, Praathibha Sripadhan, Chen Chen, Jie Lu, Tung-Wei Hou, Sujata Maiti Choudhury, Xuefeng Liu · 发表于：Cancer Research · 年份：2017 · DOI：10.1158/1538-7445.am2017-5777 · 研究领域：Virus-based gene therapy research、Cancer Research and Treatments、Molecular Biology Techniques and Applications

Abstract The E6/E7 oncogenes of the high-risk HPVs are both necessary and sufficient to immortalize HFKs and their presence and expression is required for the continued proliferation of HPV-positive cervical cancer cells. We and others have shown previously that hTERT induced by E6 and cytoskeleton alteration by E7 are critical. Both E6 and feeder cells activate telomerase, while both E7 and Rock inhibitor (Y-27632) disrupt the actin cytoskeleton and inactivate Rho. Feeders and Y-27632 to induce unlimited cell proliferation of human keratinocytes. Unexpectedly, we observed that feeders and Y-27632 could be used to establish both normal and tumor cell cultures from non-keratinocyte tissues. This culture has been termed as “conditional reprogramming”, since CR cultures stop proliferating or terminally differentiate after its removal, depending on culture conditions. The Combination of CR and Organoids ( (Matrigel, air-liquid interface (ALI)) cultures represents next generation human cancer models and functional diagnostics for cancer precision medicine as described in August 2015 in the NCI precision medicine initiative and three nature review articles (Nat Rev Cancer. 2015 Dec; Nat Rev Genet. 2015 Jul; Nat Rev Clin Oncol. 2014 Nov.). The technique is relatively simple and has been reproduced in more than 50 laboratories (including an original and independent article in Science from Massachusetts General Hospital) (Science. 2014, 346(6216):1480-6.). Importantly, the CR technolo...