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Updated: Jun 17, 2026
13:56
A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Estrogen contributes to non-pRb targeted HPV18 E7-caused cell proliferation and transformation
Xiaofei Yan1, Walayat Shah, Xu Li
1Center for Cancer Research, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Cancer Biology & Therapy
|December 17, 2009
Summary
Estrogen cooperates with high-risk human papillomaviruses (HPVs) E7 oncogene via a pRb-independent pathway in cervical carcinogenesis. This interaction enhances cell proliferation and genomic instability, promoting cancer development.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Persistent high-risk human papillomavirus (HPV) infection, particularly the E7 oncogene, is a primary cause of cervical carcinoma.
- Estrogen acts as a cofactor, synergizing with HPV E7 in cervical cancer development through pRb-dependent and pRb-independent pathways.
Purpose of the Study:
- To investigate whether estrogen contributes to high-risk HPV E7-mediated cervical carcinogenesis via the pRb-independent pathway.
- To analyze the synergistic effects of estrogen and a pRb-binding deficient E7 mutant on cellular processes relevant to cancer.
Main Methods:
- Utilized a modified E7 protein (E7(DeltaRB)) incapable of binding and degrading pRb.
- Assessed the impact of estrogen combined with PTD-HPV18E7(DeltaRB) on cell proliferation, genomic instability (centrosome duplication, chromosomal instability), and anchorage-independent growth.
- Examined protein-protein interactions between PTD-HPV18E7(DeltaRB), c-Jun, and c-Myc in the presence and absence of estrogen.
Main Results:
- Estrogen and E7(DeltaRB) synergistically enhanced cell proliferation and induced genomic instability, including abnormal centrosome duplication and chromosomal instability.
- Malignant transformation was observed, characterized by anchorage-independent growth.
- PTD-HPV18E7(DeltaRB) interacted with c-Jun and c-Myc only in estrogen-treated cells with high expression levels of these proteins.
Conclusions:
- Estrogen collaborates with HPV E7 through a pRb-independent mechanism in cervical carcinogenesis.
- The functional interaction between E7 and c-Jun or c-Myc is contingent upon reaching a critical expression threshold for c-Jun or c-Myc, facilitated by estrogen.
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