Abstract C13: Human Eag1 potassium channel expression in lung cancer biopsies.

Abstract

Introduction. Lung cancer is the most common malignancy in the world including Mexico [1, 2]. Smoking is the main risk factor for the development of different types of lung cancer, about 70–80% of lung cancer cases are associated with smoking and approximately 50% of new cancer cases are diagnosed in ex-smokers. Current therapies rarely cure the disease, and the high relapse rate with the delay in diagnosis results in a poor prognosis and overall survival rates of 10% [1]. Several ion channels are over-expressed in cancer including Kv1.3, K2p9.1, Kv10.1 (Eag1) and Kv11.1 (HERG) channels. These channels are expressed in different cell types and tumor tissues and have been shown to increase cell proliferation. Eag1 is expressed aberrantly with a high frequency (75%) in tumor cells of different histological origins including sarcomas, carcinomas of the breast, colon, and cervix. Eag1 inhibition by either astemizole, imipramine, or Eag1 specific monoclonal antibodies reduces tumor cell proliferation in vitro and in vivo [3, 4, 5]. Eag1 channels are over-expressed in lung cancer [6]. However, a detailed study of Eag1 expression in the different types of lung cancer is missing. Materials and Methods: Lung biopsies: 44 Lung biopsies were obtained from patients attending the Instituto Nacional de Enfermedades Respiratorias (National Institute for Respiratory Diseases) in Mexico City following local ethical considerations. Patients had no prior treatment (chemotherapy or radiotherapy). 37 biopsies were classified as lung cancer samples and included adenocarcinoma, epidermoid, small cell, adenosquamous and neuroendocrine tumors. 5 samples were diagnosed as inflammatory disease and 2 were form patients with thyroid carcinoma. RNA extraction was performed with TRIzol (Life Technologies, Invitrogene) according to the manufacturer's recommendation. cDNA was synthesized by reverse transcription under the manufacturer's recommendations (New England BioLabs). Eag1 gene expression was assessed by real-time PCR under the manufacturer's recommendations (Fermentas SYBR Green/ROX qPCR Master Mix). Eag1 expression in lung biopsies was compared to Eag1 basal expression in fibroblasts from normal lung (WI-38) which was given the value of 1. Results: Eag1 expression was found in 81% of the cancer biopsies while 8% of the samples did not showed changes and in 10% of the biopsies Eag1 was found to be under-expressed. Interestingly, Eag1 was over-expressed in 80% of the samples from chronic inflammation while no changes were observed in the samples from thyroid carcinoma. Conclusions: Our results suggest Eag1 as a tumor marker for different types of lung cancer and as a potential early marker of the disease. References: 1. MacKinnon C A et al. British Medical Bulletin. 95: 47–61. 2010. 2. Molina-Alavez A et al. Gaceta mexicana de oncología. 7(5): 169–173. 2008. 3. Pardo A L et al. The journal of membrane biology. 205: 115–124. 2005. 4. Blackiston J D et al. Cell cycle. 8(21): 3527–3536. 2009. 5. Camacho J. Cancer letters. 233: 1–9. 2006. 6. Hemmerlein et al. Molecular cancer. 5(41): 1–13. 2006. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C13.