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The human non-muscle α-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells

Oncogene volume 19, pages 380–386 (2000)Cite this article

Abstract

α-Actinins are actin-binding proteins important in organization of the cytoskeleton and in cell adhesion. We have cloned and characterized a cDNA from human neuroblastoma cell variants which encodes the second non-muscle α-actinin isoform designated ACTN4 (actinin-4). mRNA encoded by the ACTN4 gene, mapped to chromosome 4, is abundant in non-tumorigenic, substrate-adherent human neuroblastoma cell variants but absent or only weakly expressed in malignant, poorly substrate-adherent neuroblasts. It is also present in many adherent tumor cell lines of diverse tissue origins. Cell lines typically co-express ACTN4 and ACTN1, a second non-muscle α-actinin gene. Expression is correlated with substrate adhesivity. Analysis of deduced amino acid sequences suggests that the two isoforms may differ in function and in regulation by calcium. Moreover, ACTN4 exhibits tumor suppressor activity. Stable clones containing increased levels of α-actinin, isolated from highly malignant neuroblastoma stem cells [BE(2)-C] after transfection with a full-length ACTN4 cDNA, show decreased anchorage-independent growth ability, loss of tumorigenicity in nude mice, and decreased expression of the N-myc proto-oncogene.

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Author notes

  1. Sotiris N Nikolopoulos

    Present address: Department of Anatomy and Cell Biology, State University of New York at Syracuse, 750 East Adams Street, Syracuse, 13210, New York, NY, USA

Authors and Affiliations

  1. Department of Biological Sciences, Laboratory of Neurobiology, Fordham University, 441 East Fordham Road, Bronx, 10458, New York, NY, USA

    Sotiris N Nikolopoulos, Barbara A Spengler, June L Biedler & Robert A Ross

  2. Division of Oncology, Abramson Pediatric Research Center, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, 19104, PA, USA

    Kristin Kisselbach & Audrey E Evans

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  1. Sotiris N Nikolopoulos
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  2. Barbara A Spengler
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Nikolopoulos, S., Spengler, B., Kisselbach, K. et al. The human non-muscle α-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. Oncogene 19, 380–386 (2000). https://doi.org/10.1038/sj.onc.1203310

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