Abstract 3388: Molecular characterization of HPV type 18 cervical cancer: Upregulation of telomerase expression and induced chromosomal instability by E6 and E7 oncoproteins

Abstract

Abstract Human papillomavirus (HPV), high-risk type 18, is directly associated with approximately 98% incidence of invasive cervical cancer. Epithelial cells infected with HPV-18 become transformed and exhibit overexpression of telomerase activity and chromosomal instability. As a result of this transformation, E6 and E7 oncoproteins are perpetually expressed: E6 degrades the tumor suppressor p53; E7 inhibits the tumor suppressor pRB, leading to uncontrollable growth and the extension of telomere length. While a few studies explored the chromosomal instability induced by HPV E6 and E7 oncoproteins, the full scope of the problem has not been clearly characterized. In this research we investigated HPV-18 acquired genomic instability by E6 and E7 oncoproteins. HPV-positive cervical cancer cells, HeLa, were studied through spectral karyotyping (SKY), Giemsa banding (G-banding), telomere length, and telomerase activity using PCR ELISA assay and the TRAPeze XL Kit, which uses fluorescence energy transfer. With the use of SKY, G-banding, and chromosomal instability analysis, HeLa cells exhibited many aneuploidies. In our results, there were consistent translocations on chromosomes 4 and 11, with deletions on chromosomes 11 and 20. There were also other translocations on chromosomes 9 and 20, with deletions on chromosome 10. Additionally, copies of chromosome 5 and unidentifiable marker chromosomes were noted. Moreover, telomerase data suggest that upregulated expression of telomerase activity correlates with the increase in chromosomal instability. The aforementioned aneuploidy is demonstrative of the induced chromosomal instability from HPV-18 infection. In addition to the tumor-suppressor disruption acquired by E6 and E7 oncoproteins, HeLa cells showed gene deletion on chromosome 11. The ATM gene, which is specifically located between distal regions 11q22.3 and 11q23 of chromosome 11, is known to help identify breaks in DNA and plays a crucial role in DNA repair. Damage to the ATM gene may further play an important role in increasing cancer progression. Citation Format: Mai Do, Nichelle Cox, Naomi Long, Liliana Zarate, Chinelo Ezechukwu, Jenna Cormier, Hyun Chung, Meidrah Tyler, Judith Okoro, Diondra Harris, Victoria Vidal, Jerica Watson, Ellie Canty, Shyam Arya, Benjamin Liu, Roland Pattillo, Billy Ballard, Jay Vadgama, Eva McGhee. Molecular characterization of HPV type 18 cervical cancer: Upregulation of telomerase expression and induced chromosomal instability by E6 and E7 oncoproteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3388.