Genetic alterations and reduced expression of tumor suppressor p33(ING1b) in human exocrine pancreatic carcinoma.
OBJECTIVE
To detect the expression of p33(ING1b) protein and the change of p33(ING1b) gene in pancreatic carcinoma and to evaluate the significance of p33(ING1b) in pancreatic cell carcinogenesis.


METHODS
Pathological specimens from pancreatic carcinoma and matched non-tumor pancreatic tissues were examined for p33(ING1b) expression and mutation by immunohistochemistry, polymerase chain reaction single-strand conformation polymorphisms (PCR-SSCP) and loss of heterozygosity (LOH).


RESULTS
The rate of p33(ING1b) protein expression was 85% (34/40). A single germline missense mutation was detected in 1 of 40 tumors located at codon 215:TGC-TCC (Cys-Ser). Fourteen (60.9%) of 23 tumor samples showed LOH in all of the informative markers tested, but no mutation was detected in these tumors and only two of the informative tumors lacked expressions of p33(ING1b) protein.


CONCLUSIONS
Mutation and loss of expression are not the main reasons for the disfunction of p33(ING1b) in pancreatic carcinoma, an abnormality at the level of chromosome and/or transcription may inhibit their normal functions, potentially contributing to pancreatic cell carcinogenesis.
Yu
Guan-Zhen
GZ
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Zhu
Ming-Hua
MH
Zhu
Zhi
Z
Ni
Can-Rong
CR
Zheng
Jian-Ming
JM
Li
Fang-Mei
FM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D046790:Pancreas, Exocrine / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins