title: Expression of the ATDC (ataxia telangiectasia group D-complementing) gene in A431 human squamous carcinoma cells.
abstract: The ATDC gene was originally identified by its ability to complement the radiosensitivity defect of an ataxia telangiectasia (AT) fibroblast cell line. Because hypersensitivity to ionizing radiation is an important feature of the AT phenotype, we reasoned that ATDC may function generally in the suppression of radiosensitivity. Previous work in our laboratory focused on radiosensitization mechanisms in human squamous carcinoma (SC) cells, especially A431 cells. To establish a basis for investigating the role of ATDC in radiation-responsive signaling pathways in human SC cells, we characterized ATDC message and protein expressions in A431 cells. ATDC message expression was also compared among human epidermoid cells (A431 cells, HaCaT spontaneously immortalized human keratinocytes and normal human epidermal keratinocytes) and a normal human fibroblast cell line (LM217). We made the following major observations: (i) the relative abundance of ATDC message is substantially higher in the epidermoid cells than in the fibroblast cell line, which has a message level comparable to those reported for other fibroblast lines; (ii) ATDC is constitutively phosphorylated on serine/threonine in A431 cells; (iii) in A431 cells, ATDC is a substrate for the serine/threonine protein kinase C (PKC) but not the epidermal growth factor (EGF) receptor tyrosine kinase; and (iv) EGF decreases ATDC message and protein expressions in A431 cells after a 24-hr exposure. The phosphorylation studies suggest that the ability of ATDC to modulate cellular radiosensitivity may be mediated in part through a PKC signaling pathway.
authors.affiliation: Life Sciences Division, SRI International, Menlo Park, CA 94025, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Laderoute
authors.forename: A M
authors.initials: AM
authors.lastname: Knapp
authors.forename: C J
authors.initials: CJ
authors.lastname: Green
authors.forename: R M
authors.initials: RM
authors.lastname: Sutherland
authors.forename: L N
authors.initials: LN
authors.lastname: Kapp
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013539:Simian virus 40 / Q000502:physiology; D012867:Skin / Q000166:cytology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D011493:Protein Kinase C