Critical Role for D-type Cyclins in Cellular Transformation Induced by E6/E7 of Human Papillomavirus Type 16 and E6/E7/ErbB-2 Cooperation

Overview

Journal Cancer Sci

Specialty Oncology

Date 2007 May 11

PMID 17489986

Citations 7

Authors

Amber Yasmeen

Abdel N Hosein

Qunyan Yu

Ala-Eddin Al Moustafa

Affiliations

Soon will be listed here.

Abstract

Recently, we reported that E6/E7 of human papillomavirus (HPV) type 16 cooperates with the ErbB-2 receptor to induce cellular transformation of human normal oral epithelial (NOE) and mouse normal embryonic fibroblast (NEF) cells. Furthermore, we demonstrated that cyclin D1 is essential for this transformation induced by E6/E7 and E6/E7/ErbB-2 cooperation using cyclin D1 antisense and knockout (D1(-/-)) cells. To determine the role of all D-type cyclins (D1, D2 and D3) in E6/E7/ErbB-2 cooperation, we examined the effects of E6/E7, ErbB-2 alone and E6/E7/ErbB-2 together in NEF, NEF-D1(-/-), NEF-D2(-/-) and NEF-D3(-/-) cells. We confirm that NEF-E6/E7 and NEF-E6/E7/ErbB-2, but not NEF-ErbB-2 cells, induce colony formation in soft agar and tumor formation in nude mice. We report that E6/E7, ErbB-2 and E6/E7/ErbB-2 together all fail to induce neoplastic transformation of D1(-/-) and D2(-/-) cells in vitro and in vivo. In contrast, E6/E7/ErbB-2 together but neither E6/E7 nor ErbB-2 alone provoke cellular transformation of D3(-/-) cells. Nevertheless, D3(-/-)E6/E7/ErbB-2 cells resulted in up to a 60 and 50% decrease in colony and tumor formation in soft agar and nude mice, respectively, compared with NEF-E6/E7/ErbB-2 cells. Furthermore, using cyclin D2 small interfering RNA we inhibited tumor and colony formation of the human NOE-E6/E7-ErbB-2-transformed cell line; in contrast, cyclin D3 small interfering RNA repressed approximately 50% of colony and 40% of tumor formation of E6/E7/ErbB-2 cooperation in this cell line. These data suggest that cyclins D1, D2 and D3 (to a lesser extent) are important downstream mediators of the cellular transformation induced by E6/E7 and E6/E7/ErbB-2 cooperation in normal cells. Our data imply that anti-D-type cyclin therapies are important in the treatment of human cancers expressing high-risk HPV or HPV/ErbB-2.

Citing Articles

Coinfection of HPVs Is Associated with Advanced Stage in Colorectal Cancer Patients from Qatar.

Fernandes Q, Gupta I, Murshed K, Abo Samra H, Al-Thawadi H, Vranic S Pathogens. 2023; 12(3).

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Human Papillomaviruses-Related Cancers: An Update on the Presence and Prevention Strategies in the Middle East and North African Regions.

Fernandes Q, Allouch S, Gupta I, Elmakaty I, Elzawawi K, Amarah A Pathogens. 2022; 11(11).

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Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells Erk1/Erk2 and β-Catenin Signaling Pathways.

Gupta I, Jabeen A, Vranic S, Moustafa A, Al-Thawadi H Front Oncol. 2021; 11:630408.

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Co-presence of human papillomaviruses and Epstein-Barr virus is linked with advanced tumor stage: a tissue microarray study in head and neck cancer patients.

Al-Thawadi H, Gupta I, Jabeen A, Skenderi F, Aboulkassim T, Yasmeen A Cancer Cell Int. 2020; 20:361.

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Human Papillomaviruses and Epstein-Barr Virus Interactions in Colorectal Cancer: A Brief Review.

Fernandes Q, Gupta I, Vranic S, Moustafa A Pathogens. 2020; 9(4).

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