The human non-muscle α-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells
| Autor: | Kristin D. Kisselbach, Sotiris N Nikolopoulos, Audrey E. Evans, Robert A. Ross, June L. Biedler, Barbara A. Spengler |
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| Rok vydání: | 2000 |
| Předmět: |
Gene isoform
Cancer Research Molecular Sequence Data Mice Nude Biology Proto-Oncogene Mas Cell Line Mice Neuroblastoma Cell–cell interaction Gene expression Cell Adhesion Genetics medicine Animals Humans SOCS5 Actinin Genes Tumor Suppressor SOCS6 RNA Messenger Molecular Biology Cytoskeleton Base Sequence Microfilament Proteins Chromosome Mapping Cell Differentiation Transfection medicine.disease Cell biology Cell Transformation Neoplastic Cell culture |
| Zdroj: | Oncogene. 19:380-386 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1203310 |
| Popis: | alpha-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 alpha-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 alpha-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 alpha-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. |
| Databáze: | OpenAIRE |
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