Evidence that P12, a specific variant of P16{sup INK4A}, plays a suppressive role in human pancreatic carcinogenesis

Journal Article · Fri Jun 28 04:00:00 EDT 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.05.078· OSTI ID:22239641

Poi, Ming J. ^[1]; Knobloch, Thomas J. ^[2]; Yuan, Chunhua ^[3]; Tsai, Ming-Daw ^[4]; Weghorst, Christopher M. ^[2]; Li, Junan ^[2]

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1. Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210 (United States)
2. Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210 (United States)
3. Campus Chemical Instrument Center, The Ohio State University, Columbus, OH 43210 (United States)
4. Genomics Research Center and Institute of Biological Chemistry, Academia Sinica, Taiwan (China)

Highlights: •P12, a variant of P16{sup INK4A}, inhibits the proliferation of pancreatic cancer cells. •P12 is distinct from P16 in function and structure. •Genetic alterations of p12 are prevalent in human pancreatic carcinoma. •P12 represents a potential pancreas-specific tumor suppressor. -- Abstract: The INK4a-ARF 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 INK4a-ARF locus. Interestingly, in addition to the well-known P16{sup INK4A} (P16) and P14ARF tumor suppressors, the INK4a-ARF 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 p12 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 c-Jun, Fos, and SEI1. 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 p12 in a cohort of 40 pancreatic tumor specimens and found that p12 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.

• OSTI ID: 22239641
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 436; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENESIS
CARCINOMAS
CELL CYCLE
INACTIVATION
INHIBITION
ONCOGENES
PANCREAS
PROTEINS
STRUCTURE FUNCTIONS