Cyclin D1 is essential for neoplastic transformation induced by both E6/E7 and E6/E7/ErbB-2 cooperation in normal cells

Oncogene
Ala-Eddin Al MoustafaMoulay A Alaoui-Jamali

Abstract

More than 25% of head and neck squamous cell carcinomas (HNSCC) and 99% of cervical cancers (CxCa) are positive for high-risk human papillomaviruses (HPVs). Furthermore, the type I tyrosine kinase receptor ErbB-2 is overexpressed in at least 30% of HNSCC and CxCa. Recently, we demonstrated that E6/E7 of HPV type 16 cooperate with ErbB-2 to induce cell transformation of human normal oral epithelial (NOE) cells. This is accompanied by overexpression of cyclin D1 in NOE cells. To determine the role of cyclin D1 in E6/E7/ErbB-2 cooperation, we examined the independent effects of E6/E7 and ErbB-2, and the combined effect of E6/E7 and ErbB-2 in mouse normal embryonic fibroblast (NEF), wild type (wt), and knockout cyclin D1 (D1(-/-)) cells. We report that NEF-wt cells transduced with E6/E7 alone and E6/E7/ErbB-2 together form small and large tumors in nude mice, respectively, as well as different sized colonies in soft agar; whereas ErbB-2 alone elicits neither tumor formation in vivo nor colony formation in soft agar. More importantly, E6/E7, ErbB-2 and E6/E7/ErbB-2 together all fail to induce neoplastic transformation of cyclin D1(-/-) cells in vivo and in vitro. Furthermore, using antisense cyclin D1 we completely inhibited tumor a...Continue Reading

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Citations

Aug 4, 2010·Pathology Oncology Research : POR·Teresa WarchołPaweł P Jagodziński
Aug 9, 2011·Mediators of Inflammation·Feixin LiangHajime Sunakawa
Dec 13, 2006·Future Oncology·Amber YasmeenAla-Eddin Al Moustafa
Aug 26, 2011·Medical Hypotheses·Ala-Eddin Al MoustafaAmal Achkhar
Feb 26, 2008·Gynecologic Oncology·Ala-Eddin Al Moustafa
Dec 13, 2006·International Journal of Hygiene and Environmental Health·William W AuAyman Al-Hendy
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Felipe A CastroMichael Pawlita
Apr 12, 2005·European Journal of Cell Biology·Sibylle Mittnacht
Feb 22, 2017·Experimental Cell Research·Beverly R WuertzFrank G Ondrey
Nov 28, 2021·Life·Amr Mohamed OudaAla-Eddin Al Moustafa

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