Research Interests

Homeobox genes and cancer, BP1, gene regulation, and early detection.

Research Program

Breast Cancer: We have cloned a new human gene, BP1, which is a member of the homeobox gene family, genes important in early development. BP1 is “turned on” or activated in 80% of breast tumors. BP1 expression is associated with tumor aggressiveness. Our results strongly implicate the BP1 gene in breast cancer and suggest it may be a good target for therapy. Currently we are developing a blood test for potential early detection of BP1 activation, testing drugs that may repress BP1 and understanding the molecular effects of BP1 in breast cancer. If we can turn the gene off, perhaps patients would have a better chance of survival.

Prostate Cancer: Recently we found that BP1 is also activated in 70% of prostate tumors, where it is associated with increased cell proliferation, compared with normal prostate tissue. Studies are underway to define the molecular roles of BP1 in this type of cancer and to attempt to repress its expression.

Leukemia: BP1 is turned on in the bone marrow of 63% of acute myeloid leukemia (AML) patients. Experiments in leukemia cells confirm the idea that high BP1 levels increase cell survival. Conversely, repression of BP1 in those cells causes cell death (apoptosis); this could be the key to its action in malignancy. Moreover, we have found a drug that reduces BP1 levels in one form of leukemia. We are now examining molecular pathways affected by BP1 overexpression to identify additional therapeutic targets.

Selected Publications

• Schwartz, A.M., Man, Y-G., Rezai, M.K., Simmens, S., and Berg, P.E. BP1, a homeoprotein, is significantly expressed in prostate adenocarcinoma and is concordant with prostatic intraepithelial neoplasia (PIN). Modern Pathol. 22: 1-6, 2009.
• Awwad, R.T., Do, K., Stevenson, H., Fu, S.W., LoCoco, F., Costello, M., Campbell, C.L., and Berg, P.E. Overexpression of BP1, a homeobox gene, is associated with resistance to all-trans retinoic acid in acute promyelocytic leukemia cells. Ann. Hematol. 87: 195-203, 2008.
• Stevenson, H.S., Fu, S., Pinzone, J.J., Campbell, C.L., Simmens, S.J. and Berg, P.E. BP1 transcriptionally activates bcl-2 and inhibits TNFa-induced cell death in MCF7 breast cancer cells. Breast Cancer Research 9: R60-69, 2007.
• Man, Y-g., Fu, S.W., Schwartz, A., Pinzone, J.J., Simmens, S.J. and Berg, P.E. Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion. Breast Cancer Research & Treatment. 90: 241-247, 2005.
• Fu, S., Schwartz, A., Stevenson, H., Pinzone, J.J., Davenport, G.J., Orenstein, J.M., Gutierrez, P., Simmens, S., Abraham, J., Poola, I., Stephan, D.A. and Berg, P.E. Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer. Breast Cancer Research 5:82-87, 2003.
• Haga, S., Fu, S., Karp, J.E., Ross, D.D., Williams, D.M., Hankins, W.D., Behm, F., Ruscetti, F.W., Chang, M., Smith, B.D., Becton, D., Raimondi, S.C. and Berg, P.E. BP1, a new homeobox gene, is frequently expressed in acute leukemias. Leukemia 14: 1867-1875, 2000.