Dana M. Brantley-Sieders, Ph.D.
Assistant Professor of Cancer Biology
T-3107A Medical Center North
1161 21st Avenue South
Nashville, TN 37232-2681
Our research program focuses on molecular mechanisms that regulate breast tumor growth, tumor angiogenesis, and host-tumor interactions. Members of the Eph family of receptor tyrosine kinases regulate cell growth/survival, motility, and angiogenic remodeling during embryogenesis. More recently, several members of this family have been linked to tumor progression and neovascularization, including breast cancer.
Overexpression of one family member in particular, EphA2, correlates negatively with overall and recurrence-free survival in breast cancer patients. Our laboratory along with others has linked EphA2 signaling to Erk-dependent growth and Rac-dependent invasion in cell culture and animal models of breast cancer, as well as neovascularization and Herceptin-resistance. Moreover, EphA2 physically and functionally interacts with EGF receptor family members, including EGFR and HER2, in the context of breast cancer. More recently, we found EphA2 expression levels are highest within the Triple negative/basal-like subtype of breast cancer. Thus, EphA2 represents a new molecular target for cancer therapy, especially given its simultaneous influence on both tumor cells and the blood vessels within the surrounding microenvironment.
Ongoing studies in the laboratory focus on:
1. The role of EphA2 ligand-independent signaling in lipid metabolism in the context of breast cancer
2. The role of EphA2 signaling in Triple Negative/basal-like breast cancer growth and invasion
3. The role of EphA2 in angiocrine-mediated breast cancer growth and invasion
- Fang, WB, Brantley-Sieders, DM, Parker, MA, Reith, AD, Chen, J A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. Oncogene, 24(53), 7859-68, 2005.
- Brantley-Sieders, DM, Fang, WB, Hicks, DJ, Zhuang, G, Shyr, Y, Chen, J Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J, 19(13), 1884-6, 2005.
- Brantley-Sieders, DM, Chen, J Eph receptor tyrosine kinases in angiogenesis: from development to disease. Angiogenesis, 7(1), 17-28, 2004.
- Brantley-Sieders, D, Parker, M, Chen, J Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des, 10(27), 3431-42, 2004.
- Brantley-Sieders, DM, Caughron, J, Hicks, D, Pozzi, A, Ruiz, JC, Chen, J EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci, 117(Pt 10), 2037-49, 2004.
- Schneider, C, Strayhorn, WD, Brantley, DM, Nanney, LB, Yull, FE, Brash, AR Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. J Invest Dermatol, 122(3), 691-8, 2004.
- Muraoka, RS, Koh, Y, Roebuck, LR, Sanders, ME, Brantley-Sieders, D, Gorska, AE, Moses, HL, Arteaga, CL Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol Cell Biol, 23(23), 8691-703, 2003.
- Cheng, N, Brantley, DM, Liu, H, Lin, Q, Enriquez, M, Gale, N, Yancopoulos, G, Cerretti, DP, Daniel, TO, Chen, J Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res, 1(1), 2-11, 2002.
- Muraoka, RS, Dumont, N, Ritter, CA, Dugger, TC, Brantley, DM, Chen, J, Easterly, E, Roebuck, LR, Ryan, S, Gotwals, PJ, Koteliansky, V, Arteaga, CL Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest, 109(12), 1551-9, 2002.
- Muraoka, RS, Lenferink, AE, Law, B, Hamilton, E, Brantley, DM, Roebuck, LR, Arteaga, CL ErbB2/Neu-induced, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells. Mol Cell Biol, 22(7), 2204-19, 2002.
- Brantley, DM, Cheng, N, Thompson, EJ, Lin, Q, Brekken, RA, Thorpe, PE, Muraoka, RS, Cerretti, DP, Pozzi, A, Jackson, D, Lin, C, Chen, J Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene, 21(46), 7011-26, 2002.
- Cheng, N, Brantley, DM, Chen, J The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev, 13(1), 75-85, 2002.
- Muraoka, RS, Lenferink, AE, Simpson, J, Brantley, DM, Roebuck, LR, Yakes, FM, Arteaga, CL Cyclin-dependent kinase inhibitor p27(Kip1) is required for mouse mammary gland morphogenesis and function. J Cell Biol, 153(5), 917-32, 2001.
- Bushdid, PB, Chen, CL, Brantley, DM, Yull, F, Raghow, R, Kerr, LD, Barnett, JV NF-kappaB mediates FGF signal regulation of msx-1 expression. Dev Biol, 237(1), 107-15, 2001.
- Brantley, DM, Chen, CL, Muraoka, RS, Bushdid, PB, Bradberry, JL, Kittrell, F, Medina, D, Matrisian, LM, Kerr, LD, Yull, FE Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium. Mol Biol Cell, 12(5), 1445-55, 2001.
- Brantley, DM, Yull, FE, Muraoka, RS, Hicks, DJ, Cook, CM, Kerr, LD Dynamic expression and activity of NF-kappaB during post-natal mammary gland morphogenesis. Mech Dev, 97(1-2), 149-55, 2000.
- Muraoka, RS, Bushdid, PB, Brantley, DM, Yull, FE, Kerr, LD Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung. Dev Biol, 225(2), 322-38, 2000.
- Bushdid, PB, Brantley, DM, Yull, FE, Blaeuer, GL, Hoffman, LH, Niswander, L, Kerr, LD Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Nature, 392(6676), 615-8, 1998.
- Dana M Brantley "Apolipoprotein E synthesis by transplanted bone marrow derived cells in apolipoprotein E deficient mice." BIOS, 6774-82, 1996.
- Ph.D. in Cell Biology, Vanderbilt University (2000)