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Updated: Sep 27, 2026

In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 23, 2010
HPV16 E6 and E7 oncoproteins regulate Notch-1 expression and cooperate to induce transformation
Sanne Weijzen1, Andrei Zlobin, Mike Braid
1Cardinal Bernardin Cancer Center, Loyola University Chicago, Cancer Immunology Program, Maywood, Illinois, USA.
Abstract:
Notch receptor signaling has been implicated in cellular transformation. Notch-1 receptor expression is increased during the progression from cervical intraepithelial lesions (CIN) to invasive cervical carcinoma. Moreover, the main cellular localization of Notch-1 protein changes from cytoplasmic to nuclear with the transition from CIN III to microinvasive carcinoma. Since the E6 and E7 proteins encoded by human papilloma virus (HPV) are a causative agent of cervical carcinoma, this study determined whether E6 and E7 protein expression causes the observed upregulation in Notch-1 expression. Mouse and human primary cell lines were transfected with HPV16 E6 and E7 and Notch-1 expression and activity were analyzed. We show that Notch-1 expression and activity are upregulated by E6 and E7 independently. This was due to both transcriptional and post-transcriptional mechanisms. A protein involved in Notch processing, Presenilin-1 (PS-1), was also upregulated by E6 and E7. In the presence of E6 and E7, Notch-1 protein expression is localized in the cytoplasm. Downregulation of Notch-1 expression in a human cervical carcinoma cell line expressing E6/E7 caused striking inhibition of proliferation in vitro and tumorigenicity in vivo. These data suggest that E6- and E7-mediated upregulation of Notch signaling may contribute to disruption of regular cell growth in cervical cancer.
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