[A study on the role of DNA repair gene O6-methylguanine-DNA methyltransferase in the development of human lung cancer].
OBJECTIVE
To study the role of O(6)-methylguanine-DNA methyltransferase (hMGMT) in the development of human lung cancer.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) method was applied to measure hMGMT mRNA expression in 150 lung cancer specimens, 40 normal lung tissues, and in the peripheral mononuclear blood cells from 50 lung cancer cases and 50 normal controls. The protein expressions of p53, C-MYC and K-RAS were assessed by immuno-histochemistry. The effects of some exposure factors on the expression of hMGMT gene were analyzed. The relationships between hMGMT gene and cancer related genes p53, C-MYC and K-RAS were investigated.


RESULTS
The mRNA of hMGMT was low or absent in 49 of 150 (32.7%) lung cancer specimens, whereas 2 of 40 (5%) normal lung tissues had reduced the levels of hMGMT mRNA. The low expression of hMGMT seemed to be a risk factor of lung cancer, with a OR of 9.22 (2.05-57.65). Reduced expression levels of hMGMT mRNA were observed in 10 of 50 (20%) lung cancer patients' peripheral mononuclear blood cells, and 2 of 50 (4%) blood cells among normal controls. When investigating the exposure factors which affecting the expression of hMGMT gene, we noticed that smoking was suppressing the expression of hMGMT gene. Interestingly, over-expression of K-RAS oncogene was significantly correlated with low expression of hMGMT (P < 0.05). However, the expressions of p53 and C-myc were not correlated with the status of hMGMT gene.


CONCLUSIONS
hMGMT might play an important role in the development of human lung cancer. Low expression of hMGMT gene seemed to be a risk factor for lung cancer which could be used as a valuable biomarker on susceptibility of human lung cancers.
Lu
Jia-chun
JC
The Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China.
Shi
Lu-yuan
LY
Wu
Zhong-liang
ZL
Liao
Yong-de
YD
Zhou
Sheng
S
Wang
Xiao-yang
XY
Li
Yin-ynn
YY
Bin
Xiao-Nong
XN
Zeng
Bo-hang
BH
Chen
Jia-kun
JK
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics; D002681:China / Q000453:epidemiology; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012907:Smoking / Q000009:adverse effects; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019853:O(6)-Methylguanine-DNA Methyltransferase; D018631:ras Proteins