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
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Turpin, J; Ling, C; Crosby, E J et al. (2016) The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment. Oncogene 35:6053-6064
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