The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

Nobutake Yamamichi, Mitsue Yamamichi-Nishina, Taketoshi Mizutani, Hirotaka Watanabe, Shigeru Minoguchi, Nao Kobayashi, Satoko Kimura, Taiji Ito, Naohisa Yahagi, Masao Ichinose, Masao Omata, Hideo Iba

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Abstract

The mammalian SWI/SNF chromatin remodeling complex is composed of more than 10 protein subunits, and plays important roles in epigenetic regulation. Each complex includes a single BRG1 or Brm molecule as the catalytic subunit. We previously reported that loss of Brm, but not BRG1, causes transcriptional gene silencing of murine leukemia virus-based retrovirus vectors. To understand the biological function and biogenesis of Brm protein, we examined seven cell lines derived from various human tumors that do not produce Brm protein. We show here that these Brm-deficient cell lines transcribe the Brm genes efficiently as detected by nuclear run-on transcription assay, whereas Brm mRNA and Brm hnRNA were undetectable by reverse transcription-polymerase chain reaction analysis. These results indicate that expression of Brm is strongly and promptly suppressed at the post-transcriptional level, through processing and transport of the primary transcript or through stability of mature Brm mRNA. This suppression was attenuated by transient treatment of these cell lines with HDAC inhibitors probably through indirect mechanism. Importantly, all of the treated cells showed prolonged induction of Brm expression after the removal of HDAC inhibitors, and acquired the ability to maintain retroviral gene expression. These results indicate that these Brm-deficient human tumor cell lines carry a functional Brm gene. Treatment with HDAC inhibitors or introduction of exogenous Brm into Brm-deficient cell lines significantly reduced the oncogenic potential as assessed by colony-forming activity in soft agar or invasion into collagen gel, indicating that, like BRG1, Brm is involved in tumor suppression.

Original languageEnglish
Pages (from-to)5471-5481
Number of pages11
JournalOncogene
Volume24
Issue number35
DOIs
Publication statusPublished - 2005 Aug 18

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Keywords

  • Brm
  • HDAC inhibitors
  • Post-transcriptional regulation
  • Retroviral gene silencing
  • SWI/SNF complex

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yamamichi, N., Yamamichi-Nishina, M., Mizutani, T., Watanabe, H., Minoguchi, S., Kobayashi, N., Kimura, S., Ito, T., Yahagi, N., Ichinose, M., Omata, M., & Iba, H. (2005). The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential. Oncogene, 24(35), 5471-5481. https://doi.org/10.1038/sj.onc.1208716