American Association for Cancer Research
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Supplementary Methods, Tables 1-3, Figure 1 from Inactivating All Three Rb Family Pocket Proteins Is Insufficient to Initiate Cervical Cancer

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journal contribution
posted on 2023-03-30, 21:29 authored by Myeong-Kyun Shin, Julien Sage, Paul F. Lambert

PDF file - 370K, Genetic crosses used in this study. Supplemental Table 1: Histopathology summary in cervix for the both Rb and p107 conditionally deficient mice treated with estrogen for 6 months. (Without treatment of TAM). Supplemental Table 2:Histopathology summary in vagina for the both pRb and p130 conditionally deficient mice treated with estrogen for 6 months. Supplemental Table 3:Histopathology summary in vagina for the pRb/p107, pRb/p107/p130conditionally deficient mice treated with estrogen for 6 months. Figure S1. Evaluation of BrdU-incorporation in cervical epithelium of estrogen-treated mice.



Human papillomavirus-16 (HPV-16) is associated etiologically with many human cervical cancers. It encodes 3 oncogenes E5, E6, and E7. Of these oncogenes, E7 has been found to be the dominant driver of cervical cancer in mice. More than 100 cellular proteins have been reported to associate with HPV-16 E7, which is thought to dysregulate the cell cycle in part by binding and inducing the degradation of pRb and its related pocket protein family members, p107 and p130. The ability of E7 to inactivate the pRb family correlates with its ability to induce head and neck cancers in mice. We previously showed that the inactivation of pRb is itself not sufficient to recapitulate the oncogenic properties of E7 in cervical carcinogenesis. In this study, we evaluated mice that were deficient in multiple pocket proteins, including mice that lacked pRb, p107, and p130. Strikingly, combined loss of two or all 3 pocket proteins resulted in development of high-grade cervical intraepithelial neoplasia, but not frank cervical carcinoma. These findings strongly argue that the oncogenic properties of HPV-16 E7 in human cervical carcinogenesis may involve disruption of E7 binding proteins beyond simply the pRb family members. Cancer Res; 72(20); 5418–27. ©2012 AACR.