DNA methyltransferase 3b contributes to oncogenic transformation induced by SV40T antigen and activated Ras

Kenzo Soejima, Weizhao Fang, Barrett J. Rollins

研究成果: Article査読

77 被引用数 (Scopus)

抄録

Transcriptional silencing of tumor suppressor genes in association with DNA methylation contributes to malignant transformation. However, the specific DNA methyltransferases that initiate this process are unknown. Here we show that a de novo DNA methyltransferase, DNMT3b, substantially contributes to the oncogenic phenotype in a lung cancer model. Normal human bronchial epithelial (NHBE) cells expressing telomerase, SV40 large T antigen, and activated Ras were immortal, formed colonies in soft agar, and expressed DNMT3b. Antisense suppression of DNMT3b prevented soft agar growth. Furthermore, mouse embryo fibroblasts expressing T antigen and Ras formed soft agar colonies and large tumors, but fibroblasts from Dnmt3b-/- mice did not grow in soft agar and were much less tumorigenic in vivo. The tumor suppressor genes, FHIT, TSLC1, and RASSF1A were downregulated in transformed NHBE cells, and antisense DNMT3b treatment resulted in re-expression of FHIT and TSLC1. While expression of TSCL1 correlated with methylation of CpG dinucleotides in its promoter region, the expression of FHIT did not, suggesting that DNMT3b may silence genes by several mechanisms including direct DNA methylation or recruitment of proteins that modify chromatin. Regardless of mechanism, our data indicate that DNMT3b plays an important role in transformation.

本文言語English
ページ(範囲)4723-4733
ページ数11
ジャーナルOncogene
22
30
DOI
出版ステータスPublished - 2003 7 24
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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