Abstract 84: The role of redox state in human breast cancer progression.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC We are investigating the role of reduction-oxidation (redox) state in human breast cancer progression. Physiologic levels of oxidants and antioxidants within subcellular compartments regulate and coordinate normal cell functions. Cells in a state of redox imbalance undergo adaptation and/or altered behavior. We propose to investigate the thioredoxin 1 (TRX1) redox couple in human breast cancer progression. This molecule is known to interact with several molecules involved in breast carcinogenesis, including redox-sensitive transcription factors and estrogen receptor (ER) alpha. We hypothesize human breast cancer tissues are in a state of redox imbalance favoring a more reducing environment, and post-translational redox modifications involving TRX1, thioredoxin reductase 1 (TRXR1), and thioredoxin interacting protein (TXNIP) are involved. Preliminary data demonstrated redox imbalance in comparisons of breast cancers to surrounding tissues. TRX1 protein levels were 1.5-fold increased, while TRXR1 and TXNIP were 10-fold and 2.4-fold decreased, respectively. The redox state of TRX1 demonstrated a 4.7-fold increase in the reduced form versus the oxidized, and TRX1 activity was 2.1-fold increased. Our future plans involve analyzing redox-regulated protein subcellular distribution patterns of TRX1, TRXR1, TXNIP, and ER alpha utilizing immunohistochemistry in human breast cancer tissue microarrays varying in histological grade; determine protein levels of TRX1, TRXR1, and TXNIP, redox state of TRX1, and activities of TRX1 and TRXR1 in human breast cancer cell lines relative to normal primary epithelial cells in cell culture; and investigating the effects of modulating the extra- and intracellular redox state on cell invasion in hormone dependent/independent breast cancer cell lines. Citation Format: Tonia C. Jorgenson, Weixiong Zhong, Terry D. Oberley. The role of redox state in human breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 84. doi:10.1158/1538-7445.AM2013-84