Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon.
BACKGROUND
MLL2, an epigenetic regulator in mammalian cells, mediates histone 3 lysine 4 tri-methylation (H3K4me3) through the formation of a multiprotein complex. MLL2 shares a high degree of structural similarity with MLL, which is frequently disrupted in leukemias via chromosomal translocations. However, this structural similarity is not accompanied by functional equivalence. In light of this difference, and previous reports on involvement of epigenetic regulators in malignancies, we investigated MLL2 expression in established cell lines from breast and colon tissues. We then investigated MLL2 in solid tumors of breast and colon by immunohistochemistry, and evaluated potential associations with established clinicopathologic variables.


RESULTS
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).


CONCLUSIONS
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.
Natarajan
Thanemozhi G
TG
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC-20057, USA.
Kallakury
Bhaskar V
BV
Department of Pathology, Georgetown University Medical Center, Washington, DC-20057, USA.
Sheehan
Christine E
CE
Department of Pathology and Laboratory Medicine, Albany Medical College MC-81, 47 New Scotland Avenue, Albany, NY-12208, USA.
Bartlett
Margaret B
MB
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC-20057, USA.
Ganesan
Natarajan
N
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC-20057, USA.
Preet
Anju
A
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC-20057, USA.
Ross
Jeffrey S
JS
Department of Pathology and Laboratory Medicine, Albany Medical College MC-81, 47 New Scotland Avenue, Albany, NY-12208, USA.
FitzGerald
Kevin T
KT
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC-20057, USA.