Our research is based on my earlier discovery of a transcription factor, BP1, that is encoded by the DLX4 gene, which contains a homeobox. BP1 expression is normally seen in 0-4% of normal breast cells in low levels, but we found that BP1 is activated in 80% of breast tumors, as well as 63% of acute myeloid leukemias and 70% of prostate tumors. Others found that BP1 is activated in 47% of ovarian cancers and in non-small cell lung cancers. BP1 is also activated in a very aggressive form of breast cancer, inflammatory breast cancer (IBC), where it is activated in 100% of cases we examined.
We have evidence that BP1 can lead to metastasis since we observed BP1 positive cells in blood vessels and lymph nodes from IBC patients overexpressing BP1. When BP1 is activated, it increases cell growth and leads to increased tumor formation in mice and estrogen independence.BP1 is known to activate the following genes: BCL-2, VEGF and c-MYC, all involved in oncogenesis. In addition, BP1 is more frequently expressed in breast cancer from African American women than Caucasian women with breast cancer.
There are many important questions that need to be pursued, e.g., (1) how can we selectively turn BP1 off in cancer cells? BP1 is required for normal blood development (erythropoiesis), so would need to be targeted specifically in cancer cells. (2) What other malignancies are affected by BP1? (3) What activates BP1? In collaboration with Dr. Luciane Cavalli, we found that the DLX4 gene is amplified in about 30% of breast cancers. Estrogen also activates BP1. It is likely there are other stimulants since 80% of breast cancers overexpress BP1. In summary, there are many interesting and important lines of research involving BP1 that need to be pursued.