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Professor and Chair John Anagli, PhD Adjunct Assoc. Prof Rodrigo Andrade, Ph.D. Professor Jacob Aranda, MD, PhD Prof. Pediatrics, Pharm Cristina Artalejo, MD, PhD Assoc. Professor Michael Bannon, PhD Professor Julie Boerner, PhD Asst Prof. KCI, Pharm Chaya Brodie, PhD Adjunct Professor Dharam Chopra, PhD Prof. IEHS, Pharm Nicholas Davis, PhD Assoc. Prof. Gregory Kapatos Professor David Kessel, PhD Professor Thomas Kocarek, PhD Assoc. Prof. IEHS, Pharm Lawrence Lash, PhD Professor Karin List, PhD Asst. Prof Larry Matherly, PhD Professor Raymond Mattingly, PhD Assoc. Prof. Roy B. (Mac) McCauley, PhD Professor Kamiar Moin, PhD Subsidy Assoc.Prof. Raymond Novak, PhD Director IEHS, Pharm John Reiners, Jr., PhD Prof., IEHS, Pharm Sandra Rempel, PhD Adjunct Assoc Prof Tiziano Scarabelli, MD.PhD Adjunct Assoc Prof. David Schneider, PhD Assoc. Prof. Eugene Schoener, PhD Professor Robert B. Silver, PhD Prof. Pharm, Physiol, Radiol. Manuel Tancer, MD Prof. Psychiatry, Pharm Stanley Terlecky, PhD Assoc. Prof. Ellen Tisdale, PhD Assoc. Prof. Arun Wakade, PhD Professor Hai-Young Wu, PhD Assoc. Prof. Akio Yamazaki, PhD Prof. Ophthal., Pharm Russell Yamazaki, PhD Assoc. Prof, Assoc. Chair
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 Julie L. Boerner, Ph.D. Assistant Professor Karmanos Cancer Institute/Department of Pharmacology, Wayne State University, School of Medicine, HWCRC Rm 816, 4100 John R St., Detroit MI 48201 Tel: (313) 576-8351 FAX (313) 576-8029 E-mail: boernerj@karmanos.org Research Interests My lab is interested in the role of two tyrosine kinases, the epidermal growth factor receptor (EGFR) and c-Src, in the progression of breast cancer. The EGFR is overexpressed in about 30% of breast tumors and often correlates with poor prognosis stemming from advanced disease. The EGFR responds to its ligands, by dimerizing and inducing autophosphorylation of c-terminal tyrosines. It is the phosphorylation of these tyrosines that leads to the recruitment of cellular proteins to transduce signals through the cell, promoting biological processes such as cell growth and survival. In addition to this “autophosphorylation” of the EGFR, tyrosines on the EGFR can be phosphorylated by other kinases, including the non-receptor tyrosine kinase c-Src. Of interest, c-Src is overexpressed in over 70% of breast cancers and is co-overexpressed with the EGFR in about 30% of breast cancers. These 30% of breast cancers that overexpress both tyrosine kinases tend to correlate with advanced disease, such that patients have invasion of the tumor into the basement membrane, local and distant metastasis, and/or a shorter time to progression. These observations suggest that EGFR and c-Src may be collaborating to promote tumor progression. In that regard, tissue culture models have demonstrated that EGFR/c-Src co-overexpression in murine fibroblasts leads to synergistic increases in DNA synthesis, anchorage independent cell growth, and tumor growth in nude mice. However, whether these two molecules lead to synergistic increases in migration or invasion of either murine fibroblasts or breast cancer cell models is as yet unknown. Both EGFR and c-Src have individually been implicated in many facets of cell migration and invasion and therefore it is not unexpected that these two molecules have the ability to interact during these cellular processes. Therefore, our hypothesis is that the overexpression of EGFR and c-Src in breast cancers promotes tumor progression by modulating key regulators of migration and invasion. Specifically we are studying the overexpression of EGFR and c-Src is breast cancer using several model systems. First, inducible expression systems in breast cancer cells have been generated to overexpress the EGFR or c-Src (or various functional mutants). Second, we will use established breast cancer model cell lines that already have been characterized to have EGFR and c-Src overexpressed and use siRNA, targeted small molecule inhibitors, and inhibitory antibodies to modulate their activity and expression. From these model systems we are exploring the role of EGFR and c-Src overexpression in migration and invasion. We have found that inducing overexpression of EGFR in a “non-metastatic” breast cancer cell line increases the expression of several integrins and correlates with changes of the adhesion and subsequent invasion of the cells to fibronectin and collagen IV. However, we have not as yet observed changes in lamellipodia or filopodia formation in response to EGF or changes in migration. Work is currently under way to further explore migration and invasion in breast cancer with respect to EGFR and c-Src co-overexpression and activation. Lab personnel
Selected References Original observations in refereed journals
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