Christine Marie Eischen, Ph.D.
Associate Professor of Pathology
Associate Professor of Cancer Biology
Vanderbilt University Medical Center
Nashville , TN 37232-2561
Oncogenic and tumor suppressor pathways in tumor development
My lab investigates the genes that regulate tumor development. We study the influence tumor suppressors and oncogenes have on apoptosis, proliferation, chromosomal stability, and transformation. We have demonstrated that development to a malignancy is accelerated when there are alterations in the tumor suppressors p53 and ARF, which function to protect cells from hyperproliferative signals from oncogenes, such as Myc. Alternatively, a deficiency in the oncogene Mdm2, which normally inhibits apoptosis, results in the suppression of tumor development. Other studies are underway to further characterize these findings and elucidate novel genes, microRNAs ,and pathways that regulate transformation. Mouse models (knockout and transgenic mice), primary, immortal, and tumor cell cultures, retroviral gene transfer, biochemical purification, and gene chip and proteomic technologies are utilized in our investigations. Results from our studies will provide a better understanding of the genes and pathways that regulate tumorigenesis. Ultimately our studies will lead to a better understanding of cancer development, which will be used for improved therapeutic intervention strategies for human malignancies.
- Lushnikova, T, Bouska, A, Odvody, J, Dupont, WD, Eischen, CM Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene, 2011.
- Odvody, J, Vincent, T, Arrate, MP, Grieb, B, Wang, S, Garriga, J, Lozano, G, Iwakuma, T, Haines, DS, Eischen, CM A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis. Oncogene, 29(22), 3287-96, 2010.
- Arrate, MP, Vincent, T, Odvody, J, Kar, R, Jones, SN, Eischen, CM MicroRNA biogenesis is required for Myc-induced B-cell lymphoma development and survival. Cancer Res, 70(14), 6083-92, 2010.
- Bouska, A, Eischen, CM Mdm2 Affects Genome Stability Independent of p53. Cancer Res, 69(5), 1697-701, 2009.
- Cho, SH, Goenka, S, Henttinen, T, Gudapati, P, Reinikainen, A, Eischen, CM, Lahesmaa, R, Boothby, M PARP-14, a member of the B aggressive lymphoma (BAL) family, transduces survival signals in primary B cells. Blood, 2009.
- Eischen, CM, Lozano, G p53 and MDM2: Antagonists or Partners in Crime. Cancer Cell, 15(3), 161-2, 2009.
- Mudhasani, R, Zhu, Z, Hutvagner, G, Eischen, CM, Lyle, S, Hall, LL, Lawrence, JB, Imbalzano, AN, Jones, SN Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells. J Cell Biol, 181(7), 1055-63, 2008.
- Bouska, A, Lushnikova, T, Plaza, S, Eischen, CM Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol, 28(15), 4862-74, 2008.
- Wang, P, Lushnikova, T, Odvody, J, Greiner, TC, Jones, SN, Eischen, CM Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells. Oncogene, 2007.
- Iwakuma, T, Tochigi, Y, Van Pelt, CS, Caldwell, LC, Terzian, T, Parant, JM, Chau, GP, Koch, JG, Eischen, CM, Lozano, G Mtbp haploinsufficiency in mice increases tumor metastasis. Oncogene, 2007.
- Tompkins, VS, Hagen, J, Frazier, AA, Lushnikova, T, Fitzgerald, MP, Tommaso, AD, Ladeveze, V, Domann, FE, Eischen, CM, Quelle, DE A novel nuclear interactor of ARF and Mdm2 (NIAM) that maintains chromosomal stability. J Biol Chem, 2006.
- Wang, P, Greiner, TC, Lushnikova, T, Eischen, CM Decreased Mdm2 expression inhibits tumor development induced by loss of ARF. Oncogene, 25(26), 3708-18, 2006.
- Alt, JR, Bouska, A, Fernandez, MR, Cerny, RL, Xiao, H, Eischen, CM Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J Biol Chem, 280(19), 18771-81, 2005.
- Eischen, CM, Alt, JR, Wang, P Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma development. Oncogene, 23(55), 8931-40, 2004.
- Alt, JR, Greiner, TC, Cleveland, JL, Eischen, CM Mdm2 haplo-insufficiency profoundly inhibits Myc-induced lymphomagenesis. EMBO J, 22(6), 1442-50, 2003.
- Eischen, CM, Rehg, JE, Korsmeyer, SJ, Cleveland, JL Loss of Bax alters tumor spectrum and tumor numbers in ARF-deficient mice. Cancer Res, 62(7), 2184-91, 2002.
- Eischen, CM, Woo, D, Roussel, MF, Cleveland, JL Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol, 21(15), 5063-70, 2001.
- Eischen, CM, Roussel, MF, Korsmeyer, SJ, Cleveland, JL Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol, 21(22), 7653-62, 2001.
- Eischen, CM, Packham, G, Nip, J, Fee, BE, Hiebert, SW, Zambetti, GP, Cleveland, JL Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene, 20(48), 6983-93, 2001.
- Nip, J, Strom, DK, Eischen, CM, Cleveland, JL, Zambetti, GP, Hiebert, SW E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene, 20(8), 910-20, 2001.
- Eischen, CM, Weber, JD, Roussel, MF, Sherr, CJ, Cleveland, JL Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev, 13(20), 2658-69, 1999.
- Zindy, F, Eischen, CM, Randle, DH, Kamijo, T, Cleveland, JL, Sherr, CJ, Roussel, MF Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev, 12(15), 2424-33, 1998.
- Eischen, CM, Kottke, TJ, Martins, LM, Basi, GS, Tung, JS, Earnshaw, WC, Leibson, PJ, Kaufmann, SH Comparison of apoptosis in wild-type and Fas-resistant cells: chemotherapy-induced apoptosis is not dependent on Fas/Fas ligand interactions. Blood, 90(3), 935-43, 1997.
- Eischen, CM, Williams, BL, Zhang, W, Samelson, LE, Lynch, DH, Abraham, RT, Leibson, PJ ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis. J Immunol, 159(3), 1135-9, 1997.
- Eischen, CM, Schilling, JD, Lynch, DH, Krammer, PH, Leibson, PJ Fc receptor-induced expression of Fas ligand on activated NK cells facilitates cell-mediated cytotoxicity and subsequent autocrine NK cell apoptosis. J Immunol, 156(8), 2693-9, 1996.