Abstract 3267: Mammalian target of rapamycin (mTOR) signaling proteins are highly expressed in mamamry tumors of MMTV-TGF-β mice

Abstract

Abstract Although the roles of many signaling pathways have been investigated to determine their potential role mammary tumor (MT) development the exact molecular mechanisms of mammary tumorigenesis are still not clear. One pathway of interest with respect to cancer development is mTOR signaling which is implicated in cell growth, transcription, translation, migration, differentiation, and survival. In the present study the expression levels of proteins associated with mTOR signaling pathway in MTs and in normal mammary tissues and fat pads were determined in MMTV-TGF-β transgenic mice that develop hormone responsive MTs as they age. Mice were enrolled at 10 wks of age and were ad-libitum-fed AIN-93M diet until 73/74 wks of age. At this time MTs were removed as well as mammary tissue samples from the same location where MT initially grow. Samples were analyzed histopathologically to confirm either MT or normal mammary tissue and mice assigned to MT-positive or MT-negative groups (n=6-8 per group). Protein expression levels were then determined in MT, mammary tissue and as well as mammary fat pads (MFP). Serum insulin, IL-6 and TNF-α levels were also measured. MT- positive mice had 40% higher serum insulin level compared to MT- negative mice. In addition, serum IL-6 levels were 100% higher in MT- positive compared to the MT-negative group. Serum TNFα levels were similar in both groups. Expression levels of mTOR, p70S6K, p4EBP1, and HIF-1 proteins were significantly higher in MT of the MT-positive group compared to the corresponding tissue of MT-negative group, 64%, 106%, 129%, and 43%, respectively. On the other hand, IGF-I receptor (IGF-IR) expression level was significantly lower by 43% in the MT- positive group compared to the MT-negative group. The expression levels of p70S6K, p4EBP1, and HIF-1 proteins were similar in MFP tissues in both groups while mTOR level was lower in MFP taken from MT-positive compared to MT-negative mice. But, IGF-IR level was significantly higher, 187%, in MFP taken from the MT-positive group compared to the MT-negative group. These findings demonstrate that expression levels of the proteins involve in mTOR signaling pathway are higher in MTs compared to normal mammary tissue obtained from the site of MT origin. This supports the potential role of mTOR signaling proteins in breast cancer development and provides targets for cancer prevention. (Support CA101858, The Breast Cancer Research Foundation and The Hormel Foundation). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3267. doi:1538-7445.AM2012-3267