Abstract

The Specific Aims are:
Specific Aim 1 is designed to test the hypothesis that constitutive activation of PI3 kinase and its downstream signaling pathways mediate the alter phenotypes expressed by transformed HME cells expressing varying levels of erbB-2.
Specific Aim 2 will be used to determine the mechanisms by which other oncogenes, that are amplified and/or overexpressed in human breast cancer cells, transform HME cells. This will be done by examining, in the context of the model recently developed, the ability of specific known and candidate oncogenes to induce phenotypes that are induced by erbB-2, when overexpressed to levels similar to that of breast cancer cell lines. The phenotypes to be studied include; factor independent survival/proliferation, growth in soft agar, and invasion of basement membranes.
Specific Aim 3 is designed to examine the epigenetic consequences of overexpression of erbB-2 and other putative breast cancer oncogenes in order to identify common transcriptional events mediated by these genes, and to determine their role in the acquisition of specific altered phenotypes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070354-06
Application #
6376246
Study Section
Special Emphasis Panel (ZRG1-SSS-N (02))
Project Start
1996-07-01
Project End
2005-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
6
Fiscal Year
2001
Total Cost
$306,788
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Willmarth, Nicole E; Baillo, Andrea; Dziubinski, Michele L et al. (2009) Altered EGFR localization and degradation in human breast cancer cells with an amphiregulin/EGFR autocrine loop. Cell Signal 21:212-9
Yang, Zeng-Quan; Moffa, Allison B; Haddad, Ramsi et al. (2007) Transforming properties of TC-1 in human breast cancer: interaction with FGFR2 and beta-catenin signaling pathways. Int J Cancer 121:1265-73
Moffa, Allison B; Ethier, Stephen P (2007) Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol 210:720-31
Yang, Zeng Quan; Streicher, Katie L; Ray, Michael E et al. (2006) Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer. Cancer Res 66:11632-43
Willmarth, Nicole E; Ethier, Stephen P (2006) Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells. J Biol Chem 281:37728-37
Woods Ignatoski, Kathleen M; Dziubinski, Michele L; Ammerman, Cheryl et al. (2005) Cooperative interactions of HER-2 and HPV-16 oncoproteins in the malignant transformation of human mammary epithelial cells. Neoplasia 7:788-98
Yang, Zeng-Quan; Albertson, Donna; Ethier, Stephen P (2004) Genomic organization of the 8p11-p12 amplicon in three breast cancer cell lines. Cancer Genet Cytogenet 155:57-62
Ray, Michael E; Yang, Zeng Quan; Albertson, Donna et al. (2004) Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines. Cancer Res 64:40-7
Jia, Yifeng; Zeng, Zhao-Zhu; Markwart, Sonja M et al. (2004) Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Res 64:8674-81
Woods Ignatoski, Kathleen M; Grewal, Navdeep K; Markwart, Sonja et al. (2003) p38MAPK induces cell surface alpha4 integrin downregulation to facilitate erbB-2-mediated invasion. Neoplasia 5:128-34

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