Gene amplification of atypical PKC-binding PARD3 in radiation-transformed neoplastic retinal pigment epithelial cell lines.
Neoplastic transformation induced by ionizing radiation was studied using a human retinal pigment epithelial cell line immortalized by telomerase. Radiation-transformed cell clones were tumorigenic in athymic mice and were analyzed by G-banding and comparative genomic hybridization (CGH). Radiation-transformed cloned cell lines and cell lines derived from tumors produced in athymic nude mice following transplantation exhibited a recurrent karyotype:45,XX,der(10),-13. CGH showed an amplification of 10p11.2 and a deletion of the remaining 10p. Positional cloning of the amplified region by FISH analysis and subsequent sequence analysis of BAC clones showing amplified FISH signals identified the candidate gene PARD3. This gene also was found to be transcriptionally expressed at an increased level. The findings indicate that PARD3 may play an important role in radiation-induced carcinogenesis of RPE cells. This is the first evidence for PARD3 amplification in human cancer cells.
Zitzelsberger
Horst
H
Institute of Molecular Radiobiology, GSF-National Research Center for Environment and Health, Institute of Molecular Radiobiology, Neuherberg, Germany. Zitzelsberger@gsf.de
Hieber
Ludwig
L
Richter
Hedwig
H
Unger
Kristian
K
Briscoe
Cecilia V
CV
Peddie
Clare
C
Riches
Andrew
A
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D019572:Retinal Neoplasms / Q000209:etiology* / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D029742:Caenorhabditis elegans Proteins; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C