Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon

We examined MLL2 at both transcript and protein levels in established cell lines from breast and colon cancers. Examination of these cell lines showed elevated levels of MLL2. Furthermore, we also identified incomplete proteolytic cleavage of MLL2 in the highly invasive tumor cell lines. To corroborate these results, we studied tumor tissues from patients by immunohistochemistry. Patient samples also revealed increased levels of MLL2 protein in invasive carcinomas of the breast and colon. In breast, cytoplasmic MLL2 was significantly increased in tumor tissues compared to adjacent benign epithelium (p < 0.05), and in colon, both nuclear and cytoplasmic immunostaining was significantly increased in tumor tissues compared to adjacent benign mucosa (p < 0.05).Our study indicates that elevated levels of MLL2 in the breast and colon cells are associated with malignancy in these tissues, in contrast to MLL involvement in haematopoietic cancer. In addition, both abnormal cellular localization of MLL2 and incomplete proteolytic processing may be associated with tumor growth/progression in breast and colonic tissues. This involvement of MLL2 in malignancy may be another example of the role of epigenetic regulators in cancer.MLL2 (MLL) [Swiss-Prot: Q9UMN6] is a member of the MLL/trx family of proteins. It contains several evolutionarily conserved domains [1] including AT hooks at the N-terminus, cluster of PHD (plant homeodomain) zinc fingers associated with a bromodomain, and a SET (suppressor of variegation, enhancer of zeste, trithorax) domain at the C-terminus [1]. The full length MLL2 (MLL2FL) is an uncleaved precursor protein with a predicted molecular weight of ~290 kD. MLL2FL precursor protein undergoes post-translational proteolytic maturation, which is critical to its normal biological activity [2]. The enzyme responsible for MLL2 cleavage is taspase 1, and its consensus cleavage site (D/GVDD) is at a.a. 2063 [2]. Proteolytic cleavage generates a large N-terminus fr