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INK4 genes in pancreatic carcinoma
E Rozenblum1, M Schute, S Kern
1JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT ONCOL,BALTIMORE,MD 21205.
Oncology Reports
|May 20, 2011
Summary
The INK4 gene family, including p15, p16, and p18, regulates cell cycle. In pancreatic cancer, only p16 inactivation drives tumor growth, suggesting distinct roles for these tumor suppressor genes in vivo.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The INK4 gene family (p15, p16, p18) are structurally and functionally related, inhibiting cell cycle at G1 phase.
- INK4 genes are investigated as tumor suppressors, with p16 frequently inactivated in tumors, often alongside p15 due to deletions.
- Pancreatic carcinomas offer a model to study distinct roles of p16, p15, and p18 in tumorigenesis.
Purpose of the Study:
- To determine the in vivo functions of INK4 family members (p15, p16, p18) in pancreatic cancer.
- To investigate whether p15 and p18 are also inactivated in pancreatic tumors where p16 is mutated.
- To clarify if INK4 genes have distinct or redundant functions in tumorigenesis.
Main Methods:
- Sequence analysis of p15 and p18 genes in pancreatic carcinomas.
- Assaying for mutations and homozygous deletions in p15, p16, and p18 genes.
- Comparing inactivation patterns of INK4 genes in tumor samples.
Main Results:
- Sequence analysis revealed that p15 and p18 are not targeted for inactivation in pancreatic carcinoma.
- Inactivation of p16 alone conferred a selective growth advantage to pancreatic tumor cells.
- Homozygous deletions, a common inactivation mechanism for p16, remain unexplained.
Conclusions:
- p16 plays a distinct role in vivo in pancreatic tumorigenesis, unlike p15 and p18.
- The functional roles of INK4 family members are not redundant in the context of pancreatic cancer.
- Further research is needed to understand the mechanism of p16 inactivation via homozygous deletions.
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