Expression of MICA (MHC class I related chain gene A) and regulation by p53 and p21

LUCAS EZEQUIEL ROSSI; MERCEDES BEATRIZ FUERTES; MARÍA VICTORIA GIRART; CAROLINA INES DOMAICA; NORBERTO WALTER ZWIRNER

Rio de Janeiro, Brasil

Congreso; 13º Congreso Internacional de Inmunología; 2007

Sociedad Brasilera de Inmunología

Many tumor cells express NKG2D ligands (NKG2DLs), which triggers cytotoxicity and IFN-g secretion by NK cells, gd and ab CD8+ T lymphocytes through engagement of NKG2D. Expression of NKG2DLs such as MICA has been associated with neotransformation and the DNA damage response. This response involves the activation of p53 and p21/WAF pathways. Many tumors have mutations in p53, which contributes to tumor progression. In this work, we addressed if p53 and p21 regulate the expression of MICA in tumor cells using two experimental strategies: over expression of p53 by transient transfection of the human colon adenocarcinoma HCT116 and the human melanoma IIB-MEL-LES cell line, and analysis of p53 and p21 in a p53 or p21 knock-out cell line (the human colon adenocarcinoma HCT116). Expression of MICA was analyzed by flow cytometry and Western blot. We observed that the levels of this NKG2DL were similar in p53-transfected vs. mock-transfected cells, which indicates that the p53 anti-oncogen would not be a regulator of the expression of MICA in tumor cells. Conversely, p21-deficient cells showed slightly higher expression of MICA than wild type cells. This results indicates, although in a preliminary fashion, that the cell cycle regulator p21 could be a negative regulator of the expression of MICA. Therefore, immunotherapy strategies aimed at restoring a functional p53 pathway in tumor cells, while not exerting regulatory effects on the expression of MICA, would no exert deleterious effects on the quality of the NKG2D-mediated cytotoxic response against tumors.