title: Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth.
abstract: TIA (T-cell intracellular antigen) proteins function as DNA/RNA trans-acting regulators to expand transcriptome and proteome diversity in mammals. In the present paper we report that the stable silencing of TIA1 and/or TIAR/TIAL1 (TIA1-related/like protein 1) expression in HeLa cells enhances cell proliferation, anchorage-dependent and -independent growth and invasion. HeLa cells lacking TIA1 and/or TIAR generate larger and faster-growing epithelial tumours with high rates of proliferation and angiogenesis in nude mice xenografts. Protein array analysis of a collection of human tumours shows that TIA1 and TIAR protein expression is down-regulated in a subset of epithelial tumours relative to normal tissues. Our results suggest a link between the epigenetic control exerted by TIA proteins and the transcriptional and post-transcriptional regulation of a subset of specific genes involved in tumour progression. Taken together, these results are consistent with a role for TIA proteins as growth/tumour-suppressor genes.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/ Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain. jmizquierdo@cbm.uam.es
authors.forename: José M
authors.initials: JM
authors.lastname: Izquierdo
authors.forename: José
authors.initials: J
authors.lastname: Alcalde
authors.forename: Isabel
authors.initials: I
authors.lastname: Carrascoso
authors.forename: Raquel
authors.initials: R
authors.lastname: Reyes
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ludeña
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D039102:Poly(A)-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology*; D000074019:T-Cell Intracellular Antigen-1; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D039102:Poly(A)-Binding Proteins; D034741:RNA, Small Interfering; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human