Abstract 2766: Potassium channel expression in cervical cancer models

Abstract

Abstract Introduction. Cervical cancer is a public health problem in developing countries, and the fourth leading cause of cancer death in women worldwide. Most human cervical cancer cases are associated with high-risk human papillomavirus (HR-HPV) infection, but different cofactors including long-term use of oral contraceptives and multiple pregnancies increase the risk for cervical cancer in HPV-positive women. Ion channel expression and/or function differ between healthy and tumor cells. This alteration confers proliferation, progression, and survival advantages to tumor cells, making ion channels promising targets for cancer therapy and diagnosis. Here, we studied the mRNA expression of two potassium channels in human keratinocytes stably transfected with either E6 or both E6/E7 oncogenes of HPV16, and in a K14E7 transgenic mouse model of cervical cancer. These mice express the HPV16-E7 oncogene and develop cervical cancer after 6 months of treatment with 17β-estradiol (E2). Methods. Human normal keratinocytes and keratinocytes transfected with either E6 or E6/E7 oncogenes of HPV16 were cultured. In addition, we used the K14E7-transgenic mice-cervical cancer model; some animals were treated with E2. Continuous-release pellets delivering daily 0.05 mg of E2 were implanted into 4–6-week old female mice for either 3 months to produce low-grade cervical dysplasia or 6 months to produce cervical cancer. Total RNA extraction and subsequent quantification by qPCR of Kv3.4 and KCa3.1 mRNA channel levels were performed both from cultured cells and the mice cervical tissue. Results. Significantly higher KV3.4 and KCa3.1 channel mRNA expression was observed in keratinocytes transfected with either the E6 or E6/E7 HPV oncogenes in comparison with normal keratinocytes. In the cervical cancer mouse model, E2 treatment for 6 months increased the mRNA levels of KV3.4 and KCa3.1 channels both in the transgenic and the non-transgenic mice in comparison with the rest of the groups. The highest mRNA relative expression was observed for the KV3.4 channels in the transgenic mice displaying cervical cancer (K14E7+E2 group). Conclusion. KV3.4 channel expression may serve as a cervical cancer biomarker. This work was partially supported by Conacyt grant A1-S-9783. Citation Format: Ana Ramírez, María de Guadalupe Chávez-López, Eunice Vera, Jaime de la Garza, Patricio Gariglio, Javier Camacho. Potassium channel expression in cervical cancer models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2766.