Research Interests

Identification of a New Gene Implicated in Breast Cancer and Leukemia

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. Of particular interest in breast cancer are tumors that no longer have a protein called the estrogen receptor (ER); these tumors are termed ER negative. Women with ER negative breast cancer have a poorer prognosis and die sooner than women with ER positive breast cancer. Strikingly, BPI is activated in all of the ER negative tumors we examined. In addition, BP1 is activated disproportionately in the tumors of African American women. Moreover, we have discovered that the frequency of BP1-positive tissues increases with the progression of breast cancer. Our results strongly implicate the BP1 gene in breast cancer and suggest it may be a good target for therapy, especially in patients with ER negative tumors and in African American women with breast cancer. Current experiments are directed towards 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. In molecular experiments, we have found that when BP1 is activated in a breast cancer cell line, more cells are able to survive, an event associated with the ability to cause cancer. If we can turn the gene off, perhaps patients would have a better chance of survival.

Leukemia: BP1 is also activated 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. High BP1 levels lead to resistance to this drug. We are now examining molecular pathways affected by BP1 overexpression to identify additional therapeutic targets.

Selected Publications

1. Man, Y-g., Schwartz, A., Levine, P.H., Teal, C. and Berg, P.E. BP1, a putative signature marker for inflammatory breast cancer or tumor aggressiveness. In press, Ca. Detect. Prev.
2. 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. Br. Ca. Res. & Treat. 90: 241-247, 2005.
3. Pinzone, J.J., Stevenson, H., Strobl, J.S, and Berg, P.E.  Molecular and cellular determinants of estrogen receptor-a expression.  Mol. Cell. Biol. 24: 4605-4612, 2004.
4. 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. Br. Ca. Res. 5:82-87, 2003.
5. Fu, S., Stevenson, H., Strovel, J.W., Haga, S.B., Stamberg, J., Do, K. and Berg, P.E. Distinct functions of two isoforms of a homeobox gene, BP1 and DLX7, in the regulation of the beta-globin gene. Gene 278: 131-139, 2001.
6. 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.