PMID- 10656685 OWN - NLM STAT- MEDLINE DCOM- 20000210 LR - 20211203 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 19 IP - 3 DP - 2000 Jan 20 TI - The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. PG - 380-6 AB - 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. FAU - Nikolopoulos, S N AU - Nikolopoulos SN AD - Department of Biological Sciences, Fordham University, Bronx, New York, NY 10458 USA. FAU - Spengler, B A AU - Spengler BA FAU - Kisselbach, K AU - Kisselbach K FAU - Evans, A E AU - Evans AE FAU - Biedler, J L AU - Biedler JL FAU - Ross, R A AU - Ross RA LA - eng SI - GENBANK/U48734 PT - Journal Article PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (MAS1 protein, human) RN - 0 (Microfilament Proteins) RN - 0 (Proto-Oncogene Mas) RN - 0 (RNA, Messenger) RN - 11003-00-2 (Actinin) SB - IM MH - Actinin/analysis/genetics/*physiology MH - Animals MH - Base Sequence MH - Cell Adhesion MH - Cell Differentiation MH - Cell Line MH - Cell Transformation, Neoplastic MH - Chromosome Mapping MH - Cytoskeleton/chemistry MH - *Genes, Tumor Suppressor MH - Humans MH - Mice MH - Mice, Nude MH - Microfilament Proteins/analysis MH - Molecular Sequence Data MH - Neuroblastoma/*genetics MH - Proto-Oncogene Mas MH - RNA, Messenger/analysis EDAT- 2000/02/03 00:00 MHDA- 2000/02/03 00:01 CRDT- 2000/02/03 00:00 PHST- 2000/02/03 00:00 [pubmed] PHST- 2000/02/03 00:01 [medline] PHST- 2000/02/03 00:00 [entrez] AID - 10.1038/sj.onc.1203310 [doi] PST - ppublish SO - Oncogene. 2000 Jan 20;19(3):380-6. doi: 10.1038/sj.onc.1203310.