Anomalous overexpression of p27(Kip1) in sporadic pancreatic endocrine tumors.

BACKGROUND

Little is known about the cellular defects and molecular mechanisms leading to pancreatic endocrine tumors (PETs). p27(Kip1) is a universal cyclin-dependent kinase inhibitor (CDKI), which acts as a tumor suppressor and a negative regulator of cell cycle. From previous reports, quiescent cells show high levels of p27(Kip1) expression while neoplastic and proliferating cells show no detectable p27(Kip1) expression. We hypothesize that in malignant sporadic PETs, p27(Kip1) expression would be decreased compared with benign PETs and normal pancreatic tissue.

METHODS

Western analysis was performed on 28 PETs (7 malignant, 21 benign), 2 nonendocrine cell lines, and 5 endocrine cell lines. Signal intensities were quantitated using densitometry and standardized to normal pancreas.

RESULTS

Unexpectedly, increased p27(Kip1) expression as compared with control was seen in both benign and malignant tumors, as well as in all four pancreatic islet tumor cell lines, but not fibroblast or pituitary cell lines, evaluated. There was no difference in p27(Kip1) level between benign and malignant tumors.

CONCLUSION

This represents the first report of anomalous p27(Kip1) overexpression in sporadic PETs, and is part of a growing literature describing the paradoxical overexpression of p27(Kip1) in human tumors that includes other endocrine tumors. These studies suggest a unique molecular pathway leading to endocrine tumorigenesis.