Oncogenic role of human papillomavirus type 58 E7 variants
Refereed conference paper presented and published in conference proceedings



摘要The prevalence of cancer-causing Human papillomavirus type 58 (HPV58) is significantly common among the East Asian population. From our international epidemiological study described an HPV58 E7 variant, T20I/G63S, to be significantly associated with a higher risk for cervical cancer. Consistent with this, we found that HPV58 E7 T20I/G63S variant possess a higher oncogenic potential, particularly in degrading the tumor suppressor retinoblastoma protein (pRb) as one of the pathways through which it exerts its functional effects. Compared with the prototype and two other commonly found E7 variants, overexpression of HPV58 E7 V1 (T20I/G63S) increased the colony-forming ability of primary murine epithelial cells (P < 0.05) and enhanced the anchorage-independent growth of NIH-3T3 cells (P < 0.001), indicating a higher immortalizing power and transforming potential, respectively. The T20I/G63S variant also possessed an increased ability to degrade exogenous pRb (P < 0.001), which is a major effector pathway of E7-driven oncogenesis. Taken together, our study demonstrated a higher oncogenic potential of the HPV58 E7 T20I/G63S variant. Given that the E7 V1 (T20I/G63S) variant is commonly found in East Asia, our findings could explain in part, the high prevalence of HPV58 in cervical cancers of East Asian women, and might inform clinical screening and therapeutic management particularly for East Asian countries.
著者Siaw Shi Boon, Priscilla TY Law, Chenghua Hu, Raymond WM Lung, Grace PY Cheung, Wendy CS Ho, Zigui Chen, Paola Massimi, Miranda Thomas, David Pim, Lawrence Banks, Paul KS Chan
會議名稱EMBO | EMBL Symposium: Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture
頁次65 - 65

上次更新時間 2020-26-11 於 16:59