Overexpression of Pin1 in non-small cell lung cancer (NSCLC) and its correlation with lymph node metastases.
BACKGROUND
Pin1 isomerizes the bonds of molecules important for numerous oncogenic and cell-signaling pathways, including Bcl-2, p53, c-Jun, beta-catenin, NF-kappaB, cyclin D1, c-Myc and Raf-1. This can cause a change in conformation leading to alterations in catalytic activity, protein-protein interactions, subcellular localization and protein stability. These alterations have been shown to be associated with cell transformation and cancer progression. Pin1 is overexpressed in several different human cancers. This is the first report of Pin1 overexpression in clinical samples of non-small cell lung cancer (NSCLC).


METHODS
Protein expression levels of Pin1 in tumor and normal lung specimens were analyzed for expression of Pin1, cyclin D1, p53 and MDM2 using immunohistochemistry and compared to several clinicopathological characteristics. The mRNA expression of Pin1 was also analyzed using quantitative real-time RT-PCR and compared to clinicopathological characteristics.


RESULTS
Pin1 protein was shown to be overexpressed in NSCLC tumor samples, and correlated with lymph node positive disease and tumor stage. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression levels of Pin1 correlated with high levels of p53 or MDM2 protein, but did not show a correlation with cyclin D1. However, high levels of MDM2 correlated with cyclin D1 overexpression. Pin1 mRNA was expressed significantly more often in the tumors of smokers than of non-smokers. The relationship between the expression of protein and mRNA of Pin1 has obviously showed that protein expression isn't significantly associated with mRNA expression.


CONCLUSIONS
Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a tumor marker or as a target for cancer therapy.
He
Jie
J
Cancer Hospital and Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China. prof.hejie@263.net
Zhou
Fang
F
Shao
Kang
K
Hang
Jie
J
Wang
Hui
H
Rayburn
Elizabeth
E
Xiao
Zhi-xiong
ZX
Lee
Sam W
SW
Xue
Qi
Q
Feng
Xiao-li
XL
Shi
Su-sheng
SS
Zhang
Cui-yan
CY
Zhang
Sen
S
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase