The tripartite motif family protein 27 (TRIM27) is a transcriptional repressor that reduces induction of cell senescence by retinoblastoma-associated protein (RB1). High levels of TRIM27 expression occur in several human cancers and have been associated with poor prognosis in breast and endometrial cancers. Zoumpoulidou and colleagues from University College London, Technology Transfer CIBER of Respiratory Diseases in Barcelona, and Oregon Health and Science University, Portland, Oregon, recently examined the role of TRIM27 expression and loss of expression in cancer development.
Studies using cancer profiling arrays containing paired human tumor and normal cRNA showed that TRIM27 transcript levels were significantly elevated in common human cancers, including colon and lung cancer, compared with normal tissue (P < .001). Transcript levels were also significantly elevated in chemically induced mouse skin cancer compared with matched normal tissue (P < .001). TRIM27-deficient (TRIM27-/-) mice were resistant to chemically induced skin cancer compared with wild-type (TRIM27+/+) littermates (57% vs 8% tumor-free).
Assessment of the propensity for senescence in mouse embryonic fibroblasts showed that TRIM27-/- mouse embryonic fibroblasts had significantly enhanced senescence propensity compared with TRIM27+/+ mouse embryonic fibroblasts in response to both replicative (P < .001) and oncogenic (P < .05) stress. These responses were reduced with inactivation of murine RB1. TRIM27-/- mice were not protected from cancer caused by RB1 deletion.
As the investigators concluded, “TRIM27 expression is a modifier of disease incidence and progression relevant to the development of common human cancers and is a potential target for intervention in cancer.” ■
Zoumpoulidou G, et al: J Natl Cancer Inst 104:941-952, 2012.