EXPRESSION OF THE ATDC (ATAXIA-TELANGIECTASIA GROUP D-COMPLEMENTING) GENE IN A431 HUMAN SQUAMOUS CARCINOMA-CELLS

The ATDC gene was originally identified by its ability to complement t he radiosensitivity defect of an ataxia telangiectasia (AT) fibroblast cell line. Because hypersensitivity to ionizing radiation is an impor tant feature of the AT phenotype, we reasoned that ATDC may function g enerally 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 pathw ays in human SC cells, we characterized ATDC message and protein expre ssions in A431 cells. ATDC message expression was also compared among human epidermoid cells (A431 cells, HaCaT spontaneously immortalized h uman keratinocytes and normal human epidermal keratinocytes) and a nor mal human fibroblast cell line (LM217). We made the following major ob servations: (i) the relative abundance of ATDC message is substantiall y higher in the epidermoid cells than in the fibroblast cell line, whi ch has a message level comparable to those reported for other fibrobla st lines; (ii) ATDC is constitutively phosphorylated on serine/threoni ne in A431 cells; (iii) in A431 cells, ATDC is a substrate for the ser ine/threonine protein kinase C (PKC) but not the epidermal growth fact or (EGF) receptor tyrosine kinase; and (iv) EGF decreases ATDC message and protein expressions in A431 cells after a 24-hr exposure. The pho sphorylation studies suggest that the ability of ATDC to modulate cell ular radiosensitivity may be mediated in part through a PKC signaling pathway. (C) 1996 Wiley-Liss, Inc.