PROJECT SUIVIMARY (See Instructions): The progression of a primary mammary epithelial cell to the malignant phenotype is thought to involve multiple genetic events including the activation of dominant acting oncogenes and the loss of specific tumor suppressor genes. Of relevance to this proposal is the observation that activation of certain tyrosine kinases has been implicated in the malignant progression of a significant proportion of human breast cancers. Studies by many laboratories suggest that activation ofthe PI-3K signaling cascade plays a critical role in mammary tumor progression. The principle objective of this proposal is to elucidate the relative contribution of the EGFR family in activation of the PI-3K signaling cascade. To accomplish this objective, we plan to exploit two well characterized transgenic mouse models expressing either ErbB2 under the transcriptional control of the MMTV promoter (NDL) or under its own transcriptional control (ErbB2KI). In particular we plan to assess the relative contribution of ErbBS and its coupled downstream signaling molecules including PI-3K, Aktl and Akt2. Finally, we also will examine the in vivo role of Rab25 and its effector Rab coupling protein (RCP) in ErbB2 mammary tumor progression

Public Health Relevance

The major focus of this application is to assess the relative contribution ofthe importance of cross-talk between Integrin and EGFR family members in breast cancer progression.The results of these studies will provide important therapeutic targets to target breast cancer progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA099031-09
Application #
8534839
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
9
Fiscal Year
2013
Total Cost
$180,092
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Rehman, Sumaiyah K; Li, Shau-Hsuan; Wyszomierski, Shannon L et al. (2014) 14-3-3ýý orchestrates mammary tumor onset and progression via miR-221-mediated cell proliferation. Cancer Res 74:363-73
Chou, Chao-Kai; Lee, Heng-Huan; Tsou, Pei-Hsiang et al. (2014) mMAPS: a flow-proteometric technique to analyze protein-protein interactions in individual signaling complexes. Sci Signal 7:rs1
Cheung, Lydia W T; Yu, Shuangxing; Zhang, Dong et al. (2014) Naturally occurring neomorphic PIK3R1 mutations activate the MAPK pathway, dictating therapeutic response to MAPK pathway inhibitors. Cancer Cell 26:479-94
Chou, Ruey-Hwang; Wang, Ying-Nai; Hsieh, Yi-Hsien et al. (2014) EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4. Dev Cell 30:224-37
Hsu, Yi-Hsin; Yao, Jun; Chan, Li-Chuan et al. (2014) Definition of PKC-?, CDK6, and MET as therapeutic targets in triple-negative breast cancer. Cancer Res 74:4822-35
Davies, Alastair H; Reipas, Kristen M; Pambid, Mary Rose et al. (2014) YB-1 transforms human mammary epithelial cells through chromatin remodeling leading to the development of basal-like breast cancer. Stem Cells 32:1437-50
Du, Y; Shen, J; Hsu, J L et al. (2014) Syntaxin 6-mediated Golgi translocation plays an important role in nuclear functions of EGFR through microtubule-dependent trafficking. Oncogene 33:756-70
Gao, M; Liang, J; Lu, Y et al. (2014) Site-specific activation of AKT protects cells from death induced by glucose deprivation. Oncogene 33:745-55
Thirumurthi, Umadevi; Shen, Jia; Xia, Weiya et al. (2014) MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer. Sci Signal 7:ra71
Panupinthu, N; Yu, S; Zhang, D et al. (2014) Self-reinforcing loop of amphiregulin and Y-box binding protein-1 contributes to poor outcomes in ovarian cancer. Oncogene 33:2846-56

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