Survival Signaling in Breast Cancer

描述（由申请人提供）： 这是一份关于Akt信号在正常乳腺发育和肿瘤进展过程中乳腺血管系统中的功能和调节的授权申请。 为了更好地理解Akt信号传导对整个乳腺肿瘤的影响，我们还探索了RhoB介导的肿瘤细胞Akt通路调节的潜在差异，因为有证据表明该通路在肿瘤和间质区室之间存在显著差异。 具体目标：目标1：检测内皮细胞Akt表达对正常和荷瘤乳腺中肿瘤生长和转移以及上皮退化的影响。 目的2：评价肿瘤进展期间RhoB对肿瘤间质与上皮中Akt信号传导的调节的影响。 创新方面。 1.使用可诱导的组织特异性转基因小鼠来研究Akt信号传导在体内的作用。 2. Akt功能在正常乳腺与乳腺癌中的并行分析。 3.一种新的Akt调节剂RhoB的研究，据报道在肿瘤细胞和内皮细胞中具有相反的功能。 4.关于Akt调节的小GTP酶之间的相互作用和功能冗余的研究。

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.