Survival Signaling in Breast Cancer

描述（由申请人提供）：这是一份关于乳腺血管中Akt信号在正常乳腺发育和肿瘤进展过程中的功能和调控的资助申请。为了更好地了解Akt信号传导对整个乳腺肿瘤的影响，我们还探索了rhob介导的Akt通路在肿瘤细胞中的潜在差异，因为有证据表明该通路在肿瘤和间质室之间存在显著差异。目的1：研究内皮细胞Akt表达对正常乳腺和荷瘤乳腺肿瘤生长、转移和上皮复旧的影响。目的2：评估RhoB调节Akt信号在肿瘤进展过程中对肿瘤间质和上皮的影响。

DESCRIPTION (provided by applicant): This is a grant application about the function and regulation of Akt signaling in the mammary gland vasculature during normal mammary gland development and tumor progression. To better understand the impact of Akt signaling on the whole mammary tumor, we also explore potential differences in RhoB-mediated regulation of the Akt pathway in tumor cells because there is evidence that this pathway is significantly different between the tumor and stromal compartments. Specific Aims: Aim 1: Examine the impact of endothelial cell Akt expression on tumor growth and metastasis and on epithelial involution in the normal and tumor bearing mammary gland. Aim 2: Evaluate the impact of a RhoB modulation of Akt signaling in the tumor stroma versus epithelium during tumor progression. Innovative Aspects. 1. The use of inducible tissue specific transgenic mice to study the role of Akt signaling in vivo. 2. The side-by-side analysis of Akt function in normal versus tumor-bearing mammary glands. 3. The investigation of a novel Akt regulator, RhoB, with reportedly opposing functions in tumor cells and endothelial cells. 4. The investigation of interactions and functional redundancy between small GTPases with respect to Akt regulation.