Expression of theATDC (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.

Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy

“…We then evaluated the impact of the STING‐TRIM29 interaction blockade by SB24011 on cellular STING levels. In A431 cell line, which endogenously expresses a considerable amount of TRIM29, [17] overexpressing TRIM29 induced a decrease in the cellular STING levels, whereas TRIM29 knockdown increased STING levels (Figure 2A and B). Therefore, we monitored STING upregulation in A431 cells by blocking the STING‐TRIM29 interaction.…”