Not suprisingly, given its role as a prosurvival factor during immune responses, NF-kB activation has been observed in various inflammatory and neoplastic conditions. The Ghosh lab has ongoing projects aimed at understanding NF-kB's role in disease and we are interested in the potential of inhibiting NF-kB for theuraputic purposes.

 

NF-kB & Cancer

During the response to an infection cells of the immune system must proliferate at a rapid rate.  One important role of NF-kB during this process is in regulating the expression of genes that promote proliferation and oppose apoptosis. 

This physiologic role for NF-kB in protecting cells from apoptosis can help explain the pathologic activation of NF-kB in multiple human cancers.  In general, aberrant, constitutive activation of NF-kB has been correlated with the malignant potential of these cancers. 

 

Our group and others have shown that NF-kB activity is increased in ER-negative breast cancer tumors as well as in breast cancer cell lines.  

It is likely that activation of NF-kB allows breast tumor cells to counteract mechanisms that induce apoptosis.  Indeed, in a collaboration with researchers at Dana Farber we have shown that inhibition of NF-kB sensitizes breast cancer cells to chemotherapeutic agents.

To date, research on NF-kB and cancer has focused primarily on detecting NF-kB activity in cancer tissues and investigating how NF-kB activation contributes to cancer.  This work has established that NF-kB provides an important survival signal for many cancers and holds significant promise as a target for therapeutics. Surprisingly, however, little headway has been made in determining how NF-kB is turned on in cancer.  Consistent with our focus on understanding the mechanisms by which NF-kB is activated in response to various stimuli, we are currently exploring the mechanism of NF-kB is activation in breast cancer cells using a combination of biochemical and gene targeting approaches. 

for an extensive discussion of NF-kB and disease see the references at left and chapters 8 and 9 in "Handbook of Transcription Factor NF-kappa B"