Background: Epigenetic controls of gene expression play an important role in tumor progression. It is well established that aberrant DNA methylation is contributed for tumor progression, however, little is known about histone modification, especially methylation, for tumorigenesis. Several histone methyltransferases (HMTs) have been identified and histone lysine methylation is considered to be a critical regulator of transcription. Purpose: The aim of this study is to see the association of histone methylation on tumorigenesis through evaluating the expression of HMT genes in cancer cells. Method: We have used quantitative reverse transcription-PCR method to analyze the expression of human HMT genes, namely, Set9, Smyd3, Setdb1, Suv39h, G9a, Ezh2 and DotL1, in 5 non-small cell lung carcinoma (NSCLC) cell lines and 6 individual NSCLC specimens as well as normal human bronchoepithelial (NHBE) cells. The HMT genes were also evaluated in our transformed model of NHBE cells established by introducing human telomerase (hT), SV40 large T antigen (LT) and activated ras, sequentially. Here, introduction of hT and LT into NHBE cells had immortalized them and additional introduction of ras had fully transformed them assessed by colony formation in soft agar. Results: Most HMTs examined were upregulated in the majority of NSCLC cell lines and specimens compared to NHBE cells. Interestingly, all of the HMTs except H3-K4 HMT, Set9 and Smyd3, increased after sequential introduction of LT and ras into NHBE cells (figure), suggesting histone methylation induced by them contributed for oncogenic transformation as well as immortalization. Conclusion: Our data suggest that dysregulated expression of HMTs contribute for tumorigenesis in NSCLC, although their precise mechanisms remain to be determined.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]