[Correlation of P27 expression and localization to phosphorylated AKT in non-small cell lung cancer].
OBJECTIVE
Inactivation of tumor suppressor gene plays an important role in tumorigenesis and tumor development. Functional inactivation of the tumor suppressor gene p27 in human cancer occurs either through the loss of expression or through phosphorylation-dependent cytoplasmic mislocalization. AKT, known as protein kinase B, represents a subfamily of serine/threonine protein kinases. Activated AKT (phosphorylated AKT, p-AKT) could promote cell cycle progression by modulating many effectors in cell cycle, including the expression and localization of P27. This study was to investigate the expression and localization of P27 protein in human non-small cell lung cancer (NSCLC), and further to explore its correlation to p-AKT.


METHODS
The expression and subcellular localization of P27 and the expression of p-AKT in 80 cases of NSCLC and 35 cases of non-cancerous lung disease were detected by immunohistochemistry, and their correlations to clinicopathologic factors were statistically analyzed.


RESULTS
The total and nuclear positive rates of p27 were significantly lower in NSCLC than in non-cancerous lung disease (72.5% vs. 94.3%, 46.3% vs. 94.3%, P<0.01). There were 21 cases of NSCLC with only cytoplasmic expression of P27, while no cytoplasmic expression alone was found in 35 cases of non-cancerous lung disease (P<0.01). The nuclear positive rate of P27 was significantly higher in NSCLC without lymph node metastasis than in NSCLC with lymph node metastasis (P<0.05), and higher in well-and moderately-differentiated NSCLC than in poorly-differentiated NSCLC (P<0.05). The nuclear and cytoplasmic expression of P27 has no correlation to clinicopathologic factors of NSCLC (P>0.05). The positive rate of p-AKT was significantly higher in NSCLC than in non-cancerous lung disease (78.8% vs. 0, P<0.05); it was significantly higher in well-and moderately-differentiated adenocarcinoma than in poorly-differentiated adenocarcinoma (95.0% vs. 50.0%, P<0.05). In NSCLC, the expression of p-AKT was positively correlated to the cytoplasmic expression of P27 (r=0.437, P<0.01), but had no correlation to the nuclear expression of P27 (r=0.175, P>0.05).


CONCLUSIONS
Reduced nuclear expression or loss of expression of P27 may be associated to the development of NSCLC. The localization of P27 only in cytoplasm may be one of the characteristics of lung cancer cells. P-AKT might play a role in the cytoplasmic localization of P27, but has no correlation to its nuclear expression.
Miao
Li-Jun
LJ
Department of Respiratory Medicine, Henan Provincial Key Laboratory of Clinical Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450052, P. R. China.
Wang
Jing
J
Li
Shan-Shan
SS
Wu
Yi-Ming
YM
Wu
Yong-Jun
YJ
Wang
Xin-Chao
XC
D000293:Adolescent; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt