Increased expression of myosin light chain kinase mRNA is related to metastasis in non-small cell lung cancer.
BACKGROUND
The invasiveness of tumor cells depends in large part on their motility, which in turn depends on cytoskeletal function. A major cytoskeletal component involved in cell motility is myosin II, the classical form of myosin first identified in muscle but also expressed in nonmuscle cells. Myosin II is activated by myosin light chain kinase (MLCK), which phosphorylates it on its regulatory light chain. In this context, the contribution made by MLCK to tumor cell motility and invasiveness has been investigated extensively in vitro, but clinical evidence of such a contribution has been lacking. In the present study, therefore, we examined the role of MLCK in the metastasis of non-small cell lung cancer (NSCLC) in a clinical setting.


METHODS
We measured MLCK mRNA expression in tumor samples from 39 NSCLC patients using real-time semiquantitative reverse transcription polymerase chain reaction carried out in a LightCycler. We then correlated MLCK mRNA expression with known clinicopathological factors.


RESULTS
We found that levels of MLCK mRNA expression were higher in patients who showed disease recurrence and distant metastasis than in those who did not. Moreover, the 3-year disease-free survival rate among patients showing lower levels of MLCK mRNA expression [log10(MLCK/GAPDH) <1.4] was significantly greater than among those showing higher MLCK mRNA expression [log10(MLCK/GAPDH) > or =1.4] (87.5 vs. 50.0%; log-rank test, p = 0.021).


CONCLUSIONS
These findings are the first clinical evidence that expression of MLCK is correlated with disease recurrence and distant metastasis in NSCLC.
Minamiya
Yoshihiro
Y
Division of Thoracic Surgery, Department of Surgery, Akita University School of Medicine, Akita City, Japan. minamiya@med.akita-u.ac.jp
Nakagawa
Taku
T
Saito
Hajime
H
Matsuzaki
Ikuo
I
Taguchi
Kousei
K
Ito
Manabu
M
Ogawa
Jun-Ichi
J
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000556:secondary*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis* / Q000502:physiology*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D009219:Myosin-Light-Chain Kinase