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.


CONCLUSIONS
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.
Department of Surgery, West Los Angeles Veterans Administration Medical Center, Los Angeles, California 90095, USA.
S S
SS
Guo
X
X
Wu
A T
AT
Shimoide
J
J
Wong
M P
MP
Sawicki
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D006224:Cricetinae; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015408:Gastrinoma / Q000378:metabolism*; D006801:Humans; D007340:Insulinoma / Q000378:metabolism*; D007515:Islets of Langerhans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012016:Reference Values; D012377:Rodentia; D025521:Tumor Suppressor Proteins; D003969:Vipoma / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27