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Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human neuroblastomas

Oncogene volume 25, pages 1931–1942 (2006)Cite this article

Abstract

Differential screening of the genes obtained from cDNA libraries of primary neuroblastomas (NBLs) between the favorable and unfavorable subsets has identified a novel gene BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1). Its 350 kDa protein product possessed a Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP2) and Cdc42GAP homology domain in the COOH-terminus in addition to P-loop and a coiled-coil region near the NH2-terminus. High levels of BMCC1 expression were detected in the human nervous system as well as spinal cord, brain and dorsal root ganglion in mouse embryo. The immunohistochemical study revealed that BMCC1 was positively stained in the cytoplasm of favorable NBL cells but not in unfavorable ones with MYCN amplification. The quantitative real-time reverse transcription–PCR using 98 primary NBLs showed that high expression of BMCC1 was a significant indicator of favorable NBL. In primary culture of newborn mice superior cervical ganglion (SCG) neurons, mBMCC1 expression was downregulated after nerve growth factor (NGF)-induced differentiation, and upregulated during the NGF-depletion-induced apoptosis. Furthermore, the proapoptotic function of BMCC1 was also suggested by increased expression in CHP134 NBL cells undergoing apoptosis after treatment with retinoic acid, and by an enhanced apoptosis after depletion of NGF in the SCG neurons obtained from newborn mice transgenic with BMCC1 in primary culture. Thus, BMCC1 is a new member of prognostic factors for NBL and may play an important role in regulating differentiation, survival and aggressiveness of the tumor cells.

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Acknowledgements

We thank Shigeyuki Furuta, Shiho Hamano, Hiroyuki Inuzuka, Aiko Morohashi for technical assistance, Masayuki Fukumura, Toshihide Kanamori and Mika Kimura for helping full-length cDNA cloning, and Shigeru Sakiyama for encouragement. This work was supported in part by a Grant-in-Aid for the 2nd Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan (AN), and by Grant-in-Aid for Scientific Research (B) (AN) and for Scientific Research on Priority Areas (2) ‘Medical Genome Science’ (MO, EI, AN) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a fund from Hisamitsu Pharmaceutical Co. Inc. (AN). We also thank following hospitals and departments for providing surgical samples: First Department of Surgery, Hokkaido University School of Medicine; Department of Pediatrics, National Sapporo Hospital; Department of Pediatric Surgery, Tohoku University School of Medicine; Department of Surgery, Gunma Children's Medical Center; Department of Pediatrics, Pediatric Surgery and General Surgery, Jichi Medical University; Department of Hematology and Oncology, Saitama Children's Medical Center; Department of Pediatrics, Juntendo University School of Medicine; Department of Surgery, Kiyose Metropolitan Children's Hospital; Department of Surgery and Pathology, Chiba Children's Hospital; Department of Pediatric Surgery, Chiba University School of Medicine; Department of Pediatric Surgery, Kimitsu Central Hospital; Department of Pediatric Surgery, Niigata University School of Medicine; Department of Pediatrics and Pediatric Surgery, Aichi Medical University; Department of Pediatrics, Kyoto Prefectural Medical University; Tumor Board, Hyogo Children's Hospital; Department of Pediatrics and Pediatric Surgery, Kagoshima University School of Medicine; Department of Pediatric Surgery, Showa University School of Medicine; Department of Pediatrics, Oita University School of Medicine; Department of Pediatric Surgery, Ohta General Hospital; Department of Pediatrics, Ichinomiya City Hospital; Department of Pediatric Surgery, Osaka City General Hospital; Department of Pediatrics, Nihon University School of Medicine Itabashi Hospital; Department of Pediatric Surgery, University of Tsukuba School of Medicine.

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  1. T Machida and T Fujita: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, Japan

    T Machida, T Fujita, M L Ooo, M Ohira, E Isogai, M Mihara, D Tomotsune & A Nakagawara

  2. Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

    T Machida, T Fujita, M Mihara, M Fujimori & W Adachi

  3. Department of Pathology, Gunma University School of Medicine, Maebashi, Gunma, Japan

    J Hirato

  4. Hisamitsu Pharmaceutical Co. Inc., Tokyo, Japan

    T Hirata

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  1. T Machida
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Correspondence to A Nakagawara.

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Machida, T., Fujita, T., Ooo, M. et al. Increased expression of proapoptotic BMCC1, a novel gene with the BNIP2 and Cdc42GAP homology (BCH) domain, is associated with favorable prognosis in human neuroblastomas. Oncogene 25, 1931–1942 (2006). https://doi.org/10.1038/sj.onc.1209225

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