title: Human tumor cells segregate into radiosensitivity groups that associate with ATM and TP53 status.
abstract: We seek to determine whether cellular radiosensitivity in nineteen human colorectal tumor cell lines and three human glioblastoma tumor cell lines segregate into statistically distinct groups and whether such groups correlate with gene expression. We measure clonogenic survival in 22 cell lines that vary in radiosensitivity and in expression of selected genes: ATM, TP53, CDKN1A, 14-3-3sigma, Ki-ras and DNA mismatch repair genes. We describe and compare radiosensitivity in these cell lines by one-parameter or two parameter analysis. Radiosensitivity varies among and between colorectal tumor cell lines and glioblastoma cell lines. When compared directly using survival, or using two-parameter analysis of radiosensitivity, cell lines distribute into four statistically-significant radiosensitivity groups. These groups associate strongly with the status of two genes, ATM and TP53, but do not associate with CDKN1A, 14-3-3sigma, Ki-ras and DNA mismatch repair genes. Intrinsic cellular radiosensitivity of 22 colorectal and glioblastoma cell lines fall into four radiosensitivity groups that associate with expression of ATM and TP53. These analyses suggest multiple mechanisms underlay intrinsic cellular radiosensitivity.
authors.affiliation: Laboratory of Radiobiology Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Williams
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Cameron
authors.initials: C
authors.lastname: Koch
authors.forename: John B
authors.initials: JB
authors.lastname: Little
mesh_terms: D048948:14-3-3 Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005092:Exonucleases / Q000235:genetics; D005095:Exoribonucleases; D015870:Gene Expression; D011905:Genes, ras / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human