Objective: Although the kinase insert domain-containing receptor (KDR) gene play an very important role in the metastasis of cancer and is also as one of the molecular targets used in cancer therapy, mutation in the tyrosine kinase (TK) domain of the KDR gene has not been reported. Here we detected the mutations and polymorphisms in the TK domain of KDR gene in human lung cancer patients and to give the basic evidence and clue for cancer prevention and target therapy. Methods: The entire sequence of exons 21, 22, 23 and 27 (which contain the coding sequence of tyrosine phosphorylation) in the TK domain of KDR gene in the patients with lung cancer and control healthy individuals were assayed by PCR and DNA sequencing. We also analyzed one non-coding single nucleotide polymorphisms (SNPs) in the KDR gene. Results: No mutations were found in exon 22, 23 and 27. One heterozygous mutation of c.+2837 in exon 21 was found at a frequency of 2.08% (2/96) in the patients with lung cancer and none were detected in the healthy control individuals. The mutation was from a G to a A resulting in substitution of arginine with histidine residue. Conclusion: Our data suggested that we should focus on the mutation or SNP in the other regions or the expression levels of KDR gene, and the function of c.+2837 mutation of KDR gene may be needed further study in the future.
Shejuan An Zhihong Chen Jian Su Jiaying Lin Ying Huang Hongyan Tang Yilong Wu
Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.
