Abstract B45: Gene expression alteration in chronic hypoxic MCF7 breast cancer cell line.

Abstract

Abstract Background: As solid tumors outgrow their vasculature, areas of low oxygen concentration arise where the oxygen demand surpasses supply. Hypoxia plays a significant role in tumor progression and aggressiveness. It is also implicated in therapy resistance to radiotherapy and chemotherapy. Objective: The aim of this study is to characterize the changes in gene expression associated with chronic hypoxia in MCF7 breast cancer cell line with the goal of identifying a possible biomarker for hypoxia in breast cancer. Methodology: Breast cancer cells (MCF7) were exposed to 8-hour hypoxic episodes (<1% oxygen) three times a week for a total of 38 episodes. The alterations in gene expression were measured using the real-time based PCR array technology after 19 and 38 episodes of hypoxia and compared to normoxic cells. Chemoresistance of hypoxic cells toward doxorubicin was assessed using MTT cell proliferation assay. Results: Marked gene expression changes were indentified after 19 and 38 episodes of hypoxia. Only few changes were common in both stages with most genes rebounding at the level of 38 episodes. A notable gene (HNF4A) has been up-regulated by 2 folds after 19 hypoxic shots and further up-regulated by 6.43 folds after 38 hypoxic shots. The half maximal inhibitory concentration (IC50) of doxorubicin in MCF7 cells has increased by 1.5 folds after 19 episodes of hypoxia and quadrupled after 35 episodes compared to normoxic cells. Conclusions: This study provide evidence that exposing cells to prolonged periods of hypoxia (weeks) results in different expression changes than those induced by short-term hypoxia (<72 hours). It also confirms induction of chemoresistance by chronic hypoxia. Finally, it proposes HNF4A as a potential biomarker for hypoxia in breast cancer and as a main player in the cellular response to chronic hypoxia. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B45. Citation Format: Malek A. Zihlif, Feda’ Hisham Hamdan. Gene expression alteration in chronic hypoxic MCF7 breast cancer cell line. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B45.