|D. Joseph Jerry
Associate Professor of Veterinary and Animal Sciences, University of Massachusetts
Ph.D.: Pennsylvania State University
Tumor Suppressor Genes and the Cellular Basis for Susceptibility to Breast Cancer
Loss of specific tumor suppressor genes has been demonstrated in both familial and sporadic breast cancers; however, the underlying genetic and cellular basis of susceptibility in breast tissue is poorly understood. Critical phases of breast development have been identified during which susceptibility to breast cancer is increased. In contrast, the differentiation of the breast epithelium that takes place during a single full-term pregnancy diminishes life-time risk of breast cancer by half. It is the goal of my laboratory to define the molecular events that regulate susceptibility of the breast epithelium and develop strategies to intervene in these pathways.
We have observed changes in the expression and function of the p53 tumor suppressor gene in breast tissues at different stages of development. Therefore, a major focus of the laboratory is to discover the normal cellular mechanisms that regulate p53 expression and function. A variety of mammary epithelial cell lines and mice bearing knockout alleles or transgenes are used in studies to identify factors that regulate p53 activities in apoptosis, cell cycle arrest, and suppression of tumors. More recently, we have begun to look at epigenetic changes in tumor cells that can be reversed by nuclear transplantation. Through the combined use of transgenic animals and contemporary techniques in molecular and cellular biology, we are defining the developmental biology of the breast epithelium itself, while providing both a genetic and cellular basis for susceptibility to breast cancer.
Becker, K.A., Lu, S.L., Dickinson, E.S., Dunphy, K.A., Mathews, L., Schneider, S.S. and Jerry, D.J. 2005. Estrogen and progesterone regulate radiation-induced p53 activity through TGF-? dependent pathways. Oncogene (Epub June 6, 2005)
Blackburn, A.C., McLary, S.C., Naeem, R., Luszcz, J., Stockton, D.W., Donehower, L.A., Mohammed, M., Mailhes, J.B., Soferr, T., Naber, S.P., Otis, C.N., and Jerry, D.J. 2004. Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain. Cancer Res. 64:5140-5147.
Blackburn, A.C., Brown, J.S., Naber, S.P., Otis, C.N. Wood, J.T., and Jerry, D.J. 2003. BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice. Cancer Res. 63:2364-2368, 2003.
Minter, L.M., Kuperwasser, C.K., Dickinson, E.S., and Jerry, D.J. 2002. Cell-cycling status of mammary epithelial cells predicts p53 responsiveness to
Jerry, D.J., Minter, L.M., Becker, K.A.., and Blackburn, A.C. 2002. Hormonal control of p53 and chemoprevention. Br. Cancer Res. 4:91-94.
Blackburn, A.C. and Jerry, D.J. 2002. The use of animal models to study the role of the p53 tumor suppressor in breast cancer. Br. Cancer Res. 4:101-111.
Jerry, D.J., Dickinson, E.S., and Roberts, A.L. 2002. Regulation of apoptosis during mammary involution by the p53 tumor suppressor gene. J. Dairy Sci.
Jerry, D.J. and Ozbun, M.A. 2002. P53 tumor suppressor gene: structure and function. In: Encyclopedia of Cancer. Editor: Joseph Bertino. Academic
Kasinathan, P., J. G. Knott, P. N. Moreira, A. S. Burnside, D. J. Jerry and J. M. Robl (2001). "Effect of fibroblast donor cell age and cell cycle on development of bovine nuclear transfer embryos in vitro." Biol Reprod 64(5): 1487-93.
Kasinathan, P., J. G. Knott, Z. Wang, D. J. Jerry and J. M. Robl (2001). "Production of calves from G1 fibroblasts." Nat Biotechnol 19(12): 1176-8.
Kuperwasser, C. Hurlbut, G.D., Kittrell, F.S., Medina, D., Dickinson, E.S., Naber, S.P. and Jerry, D.J.(2000) "Development of spontaneous mammary tumors in BALB/c p53-heterozygous mice: A model for Li-Fraumeni syndrome." Am. J. Pathol. 157:2151-2159
Kuperwasser, C., Pinkas, J., Hurlbut, G.D., Naber, S.P., and Jerry, D.J. (2000) "Cytoplasmic sequestration and functional repression of p53 in mammary epithelium is reversed by hormonal treatment." Cancer Res. 60:2723-2729.
Jerry, D.J., Kittrell, F.S., Kuperwasser, C., Laucirica, R., Dickinson,E.S., Bonilla, P.J., Butel, J.S., and Medina, D. (2000) "A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development." Oncogene 19:1052-1058.
Pinkas, J., Butel, J.S., Medina, D. and Jerry. D.J. (1999) "Alternative splicing of the p53-binding domain in mdm2 during mammary tumorigenesis in the mouse". Int. J. Cancer 81:292-298.
Jerry, D.J., Kuperwasser, C., Downing, S.R., Pinkas, J., He., C., Dickinson, E., Marconi, S. and Naber, S.P. (1998) "Delayed involution of mammary epithelium in BALB/c-p53null mice." Oncogene 17, 2305-2312.
Medina, D., Stephens, L.C., Bonilla, P.J., Hollmann, C.A., Schwahn, D., Kuperwasser, C., Jerry, D.J., Butel, J.S. and Meyn, R.E. (1998) "Radiation-induced tumorigenesis in preneoplastic mouse mammary glands in vivo: Significance of p53 status and apoptosis." Mol. Carcinogenesis 17 (18), 2305-2312.
Zawada, W.M., Cibelli, J.B., Choi, P.K., Clarkson, E.D., Goluike, P.J., Witta, S.E., Bell, K.P., Kane, J., Ponce de Le—n, F.A., Jerry, D.J., Robl, J.M., Freed, C.R. and Stice, S.L. (1998) "Somatic cell cloning-produced transgenic bovine neurons for transplantation in Parkinsonian rats." Nat. Med. 4, 569-574.
Cibelli, J.B., Stice, S.L., Golueke, P.J., Kane, J.J., Jerry, J., Blackwell, C., Ponce de Ležn, F.A. and Robl, J.M. (1998) "Cloned transgenic calves produced from non-quiescent fetal fibroblasts." Science 280, 1256-1258.