MNT and CCDC6 in cutaneous T cell lymphoma cells

Abstract

ABSTRACT : MYC oncoprotein belongs to a protein-interaction network that include proteins of the MXD family, as both MYC and MXD proteins have a common interaction partner: MAX. MYC is deregulated in up to 60% of human tumors and has a crucial role in the initiation and progression of cancer. Unfortunately, MYC has proven to be a difficult therapeutic target. For this reason, the study of the MYC network proteins is important. The most relevant MXD proteins is MNT, because it is ubiquitously expressed and is deregulated in tumors. MNT is labelled as tumor suppressor being an antagonist of MYC, but in some models it cooperates with MYC promoting cell proliferation and survival. Our lab has previously demonstrated a MNT-CCDC6 interaction. CCDC6 is a protein involved in DNA damage repair and a tumor suppressor. Thus, I have studied the activity of MNT and CCDC6 as they can provide the basis for alternative strategies to impair MYC activity in cancer. One of the tumors showing frequent MNT deregulation or deletions is cutaneous T cell lymphoma (CTCL) and thus we focused in CTCL cell lines. First, using Western Blot, I have compared MNT and CCDC6 expression in several human lymphoma cells. Then I have performed co-immunoprecipitation experiments to investigate the MNT CCD6 interaction in the cell lines with significant expression of both genes. I have also silenced MNT with short-hairpin methodology, using lentiviral vectors to analyze the effect of MNT depletion on proliferation of the lymphoma cells. Silencing was confirmed by western blot. An increase of proliferation was detected in at least once cell line.