
<ArticleTitle>Activated <prot>Notch1</prot> signaling cooperates with papillomavirus oncogenes in transformation and generates resistance to apoptosis on matrix withdrawal through PKB/Akt.</ArticleTitle>
<AbstractText>Invasive cervical tumors, a major subset of human epithelial neoplasms, are characterized by the consistent presence of papillomavirus oncogenes 16 or 18 E6 and E7 products. Cervical tumors also consistently exhibit cytosolic and nuclear forms of <prot>Notch1</prot>, suggesting the possible persistent activation of the Notch pathway. Here we show that activated <prot>Notch1</prot> synergizes with papillomavirus oncogenes in transformation of immortalized epithelial cells and leads to the generation of resistance to anoikis, an apoptotic response induced on matrix withdrawal. This resistance to anoikis by activated <prot>Notch1</prot> is mediated through the activation of <prot>PKB</prot>/<prot>Akt</prot>, a key effector of activated <prot>Ras</prot> in transformation. We suggest that activated Notch signaling may serve to substitute for the lack of activated <prot>Ras</prot> mutations in the majority of human cervical neoplasms.</AbstractText>
