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  • Original Paper
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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 volume 24, pages 5471–5481 (2005)Cite this article

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.

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Acknowledgements

We thank Japan Energy Corporation and Fujisawa Corporation for supplying CHAP31 and FK228, respectively. Anti-Brm antibody was supplied by Kumamoto Immunochemical Laboratory, Transgenic Inc., Kumamoto, Japan. We thank Drs Yana and Seiki (Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo) for technical advice regarding the tumor invasion assay, Drs Kameda and Sugiyama (Department of Biochemistry, Akita University School of Medicine) for useful suggestion in producing pSSSP vector, Dr Kitamura (Division of Cellular Therapy, Institute of Medical Science, University of Tokyo) for providing us the PLAT packaging cell line, and Dr Yoshida for fruitful discussion concerning HDAC inhibitors. SW13 and G401 were obtained from Japanese Collection of Research Bioresources, and PA-1 and A549 were obtained from Cell Resource Center for Biomedical Research, Tohoku University. We were also grateful to Dr Niwa (Riken Center) for his gift of EB5 (embryonic stem cell), and also grateful to N Hashimoto and K Takeda for assistance in preparing this paper. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Cultures, Sports, Science, and Technology of Japan.

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  1. Department of Microbiology and Immunology, Division of Host–Parasite Interaction, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Nobutake Yamamichi, Mitsue Yamamichi-Nishina, Taketoshi Mizutani, Hirotaka Watanabe, Shigeru Minoguchi, Nao Kobayashi, Satoko Kimura, Taiji Ito & Hideo Iba

  2. Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    Nobutake Yamamichi, Naohisa Yahagi & Masao Omata

  3. Second Department of Internal Medicine, Wakayama Medical College, Wakayama, Japan

    Masao Ichinose

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  1. Nobutake Yamamichi
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Correspondence to Hideo Iba.

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Yamamichi, N., Yamamichi-Nishina, M., Mizutani, T. et al. 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, 5471–5481 (2005). https://doi.org/10.1038/sj.onc.1208716

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