Email: jjerry@vasci.umass.edu
J. Jerry Vet & Animal Sciences Web Site
J. Jerry PVLSI Web Site

Ph.D.: Pennsylvania State University
Postdoctoral Training: Jackson Laboratory; Baylor College of Medicine

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.

Representative publications:

Lu, S., Becker, K.A., Hagen, M.J., Yan, H., Roberts, A.L., Mathews, L.A., Schneider, S.S., Siegelmann, H.T., Tirrell, S.M., MacBeth, K.J., Blanchard, J.L. and Jerry, D.J. 2008. Transcriptional responses to estrogen and progesterone in Mammary gland identify networks regulating p53 activity. Endocrinology. (E-pub on June 12)

Dunphy, K.A., Blackburn, A.C., Yan, H., OConnell, L.R., and Jerry, D.J. 2008. Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice. Br. Cancer Res. 12;10(3):R43.

Bappaditya Samanta, Haoheng Yan, Nicholas O. Fischer, Jing Shi, D. Joseph Jerry, Vincent M. Rotello. 2008. Protein-passivated Fe3O4 nanoparticles: low toxicity and rapid heating for thermal therapy. J. Materials Chem. 18:1204-1206 Cover image.

Koch, J.G., Gu, X.., Han, Y., El-Naggar, A.K., Olson, M.V., Medina, D., Jerry, D.J., Blackburn, A.C., Peltz, G., Amos, C.I., and Lozano, G. 2007.  Mammary tumor modifiers in BALB/cJ mice heterozygous for p53. Mamm. Genome 18(5):300-9.

Jerry, D.J. 2007. Roles for estrogen and progesterone in breast cancer prevention. Br. Cancer Res. 9(2):102. (Invited editorial)

Blackburn, A.C., Hill, L.Z., Roberts, A.L., Wang, J., Aud, D., Jung, J., Nikolcheva, T., Allard, J., Peltz, G. Otis, C.N., Cao, Q. J., Ricketts, R. St. J., Naber, S.P., Mollenhauer, J., Poustka, A., Malamud, D., and Jerry, D.J. 2007. Genetic mapping in mice identifies DMBT1 as a candidate modifier of breast cancer risk. Am. J. Pathol. 170:2030-41.

Tu, Yifan, Jerry, D.J., Pazik, B. And Schneider, S.S. 2005. Sensitivity to DNA damage is a common component of hormone based strategies for protection of the mammary gland. Mol. Cancer Res. 3:435-442.

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 24:6345-6353.


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 D.J. Jerry (2002) Cell-cycling status of mammary epithelial cells predicts p53 responsiveness to gamma-radiation. Development 129:2997-3008. Pub Med Abstract

Jerry D.J., Minter L.M., Becker K.A., and A.C. Blackburn (2002) Hormonal control of p53 and chemoprevention. Br. Cancer Res. 4:91-94. PubMed Abstract

Poothapillai K, Knott J.G., Wang Z., Jerry D. J., and J.M. Robl (2001) Production of calves from G1 fibroblasts. Nat. Biotechn. 19:1176-1178. PubMed Abstract

Kuperwasser C., Hurlbut G.D., Kittrell F.S., Medina D., Dickinson E.S., Naber S.P. and D.J. Jerry (2000) Development of spontaneous mammary tumors in BALB/c p53-heterozygous mice: A model for Li-Fraumeni syndrome. Am. J. Pathol. 157:2151-2159. PubMed Abstract

Kuperwasser C., Pinkas J., Hurlbut G.D., Naber S.P., and D.J. Jerry (2000) Cytoplasmic sequestration and functional repression of p53 in mammary epithelium is reversed by hormonal treatment. Cancer Res. 60:2723-2729. PubMed Abstract

Jerry D.J., Kittrell F.S., Kuperwasser C., Laucirica R., Dickinson E.S., Bonilla P.J., Butel J.S., and D. Medina (2000) A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene 19:1052-1058. PubMed Abstract

Pinkas J., Butel J.S., Medina D. and D.J. Jerry (1999) Alternative splicing of the p53-binding domain in mdm2 during mammary tumorigenesis in the mouse. Int. J. Cancer 81:292-298. PubMed Abstract

Jerry D.J., Kuperwasser C., Downing S., Pinkas J., He C., Dickinson E.S., Marconi S., and S.P. Naber (1998) Delayed involution of the mammary epithelium in BALB/c-p53null mice. Oncogene 17:2305-2312. PubMed Abstract