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The proto-oncogene Bcl6 inhibits apoptotic cell death in differentiation-induced mouse myogenic cells

Oncogene volume 18, pages 467–475 (1999)Cite this article

Abstract

The Bcl6 gene is located at chromosomal band 3q27, a breakpoint for translocation that frequently occurs in B cell lymphomas. Bcl6 has been found to be preferentially expressed in germinal center B cells, and expression of this gene has been shown to be essential for germinal center formation in vivo. The physiological function of Bcl6 and its role in lymphomagenesis, however, are not yet known. Since significant expression of Bcl6 has been demonstrated in skeletal muscle, we have utilized a differentiation-inducible mouse myogenic cell line, C2C12, to elucidate the function of the Bcl6 gene product. Expression of Bcl6 mRNA was very low in growing myocytes, but was increased in differentiating myocytes cultured in serum-starved medium. Incubation of these cells with cytokines or chemicals that are known to block differentiation suppressed this increased Bcl6 message abundance, indicating that Bcl6 induction is related to the process of terminal differentiation in muscle cells. While a fraction of myocytes is known to undergo apoptosis after serum-starvation to induce differentiation, adenovirus-mediated overexpression of Bcl6 enhanced the viability of the differentiating cells by preventing the apoptosis. High levels of Bcl6 antisense mRNA expression induced substantial apoptosis during the differentiation of C2C12 cells, but this was effectively prevented by infection with adenovirus that expressed Bcl6 sense mRNA. These results indicate that Bcl6 acts to prevent apoptotic cell death in differentiating myocytes. The deregulation of expression of this anti-apoptotic gene may also contribute to the development of B cell lymphomas.

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Acknowledgements

We thank Drs Izumu Saitoh and Yumi Kanegae (Laboratory of Molecular Genetics, The Institute of Medical Science, University of Tokyo) for the adenovirus vector and the recombinant adenovirus AxCALacZ, Dr Shousei Yoshida (Department of Molecular Genetics, National Institute of Neuroscience) for C2C12 cells and myogenin cDNA, Dr Kenneth Walsh (Division of Cardiovascular Research, St Elizabeth's Medical Center and Tufts University School of Medicine) for 10T1/2 and 10T1/2-MyoD cells, Dr Andrew B Lassar (Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School) for MyoD cDNA, Dr Jun-ichi Miyazaki (Department of Molecular Embryology Institute of Development, Aging and Cancer, Tohoku University) for pCAGGS, Dr Seiji Okada (Division of Developmantal Genetics, Center for Biological Science, Chiba University School of Medicine) for bcl2 cDNA and Dr Shigeo Ohta (Nippon Medical School, Kawasaki, Japan) for rat bclxL cDNA. We also thank Dr Junko Nishio and Ms Kaori Okada for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research to Tohru Miki and Shinsaku Hirosawa, from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. The First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, 113-8519, Tokyo, Japan

    Takashi Kumagai, Tohru Miki, Tetsuya Fukuda, Nobuyuki Miyasaka & Shinsaku Hirosawa

  2. The School of Allied Health Science, Faculty of Medicine, Tokyo Medical and Dental University, 113-8519, Tokyo, Japan

    Mika Kikuchi & Ryuichi Kamiyama

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  1. Takashi Kumagai
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Kumagai, T., Miki, T., Kikuchi, M. et al. The proto-oncogene Bcl6 inhibits apoptotic cell death in differentiation-induced mouse myogenic cells. Oncogene 18, 467–475 (1999). https://doi.org/10.1038/sj.onc.1202306

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