ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human glioma cell lines and present in vitro anti-oncogenic and chemoresistant properties.
Human oligodendrogliomas are chemosensitive gliomas usually characterized by a loss of heterozygosity in the large distal regions of the short arm of chromosome 1 (1p LOH). Chemoresistant astrocytomas do not have this genetic signature, suggesting that the 1p arms may contain anti-oncogene and/or genes enabling chemoresistance. We have focused here on two human 1p-distal genes, ATAD 3A and ATAD 3B (1p36-33), and analyzed their gene products in normal human cell lines and tissues and in glioma-derived human cell lines. Using specific anti-peptide antibodies, we have found that ATAD 3A is ubiquitously expressed, whereas ATAD 3B is expressed in embryonic tissues, adult germinative zone and in astrocytoma cell lines but it is not expressed in oligodendroglioma cell lines or in the adult cortex. Furthermore, we have found that human glioma cell lines overexpressing or underexpressing ATAD 3A and ATAD 3B, show modified cell growth, anchorage-independent growth, and chemoresistance to doxorubicin and other genotoxic drugs. These results demonstrate the potential for ATAD 3B as a putative marker in discriminating astrocytomas from oligodendrogliomas. We also have shown that the loss of ATAD 3A/3B may be involved in the transformation pathway and the chemosensitivity of oligodendrogliomas.
Hubstenberger
Arnaud
A
Laboratoire Transduction du Signal EMI104 INSERM/CEA/UJF DRDC Centre d'étude Nucléaire, 17 Ave des Martyrs, 38054 Grenoble cedex, France.
Labourdette
Gérard
G
Baudier
Jacques
J
Rousseau
Denis
D
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D000818:Animals; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D019556:COS Cells; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics; D009837:Oligodendroglioma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics
C549686:ATAD3A protein, human; C519737:ATAD3B protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities