Biochemical and Biophysical Research Communications, 28 June 2013, Vol.436(2), pp.217-222
The locus plays a central role in the development of pancreatic tumors as evidenced by the fact that up to 98% of pancreatic tumor specimens harbored genetic alterations at the locus. Interestingly, in addition to the well-known P16 (P16) and P14ARF tumor suppressors, the locus in pancreas encodes another protein, P12, whose structure, function, and contributions to pancreatic carcinogenesis remain to be elucidated. In the current study, we demonstrated that over-expression of in human pancreatic cancer cells led to cell arrest at the G1 phase and such cell cycle arrest was related to down-regulation of a number of oncogenes, such as , , and . Furthermore, unlike P16, P12 did not retain any cyclin-dependent kinase 4 (CDK4)-inhibitory activity. Instead, P12 exhibited a transactivating activity not found in P16. We also examined the genetic status of in a cohort of 40 pancreatic tumor specimens and found that alteration was prevalent in pancreatic tumors with an incidence of 70% (28/40). These results support that P12 is a tumor suppressive protein distinct from P16, and its genetic inactivation is associated with pancreatic carcinogenesis.
P12 ; P16ink4a ; The Ink4a-ARF Locus ; Tumor Suppression ; Pancreatic Cancer ; Biology ; Chemistry ; Anatomy & Physiology
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