The tumor and metastasis suppressor RECK gene encodes a 110 kDa glycoprotein anchored to the cytoplasmic membrane by a GPI anchor. The RECK gene mRNA is abundantly expressed in many human normal tissues, whereas its expression is suppressed in both tumor cell lines and in oncogenically transformed fibroblasts, including fibroblasts transformed by the c-myc gene, suggesting that RECK is a physiological target for c-Myc. Deregulated expression of the c-myc proto-oncogene contributes to malignant progression of a variety of human tumors, such as breast, colon, lung, and cervical carcinomas, osteosarcomas, glioblastomas, and myeloid leukemias. Several biological functions of c-Myc have been described, including induction of programmed cell death, inhibition of terminal differentiation, regulation of the efficiency of rRNA maturation and potentiation of cell cycle progression. We have previously described that inhibition of the RECK gene expression by c-Myc occurs through alterations in the transcriptional activity of this gene and that RECK repression parallels c-myc induction by serum. The mechanisms by which c-Myc is able to repress RECK expression is yet obscure. In order to address this question, we used cycloheximide and trichostatin A in NIH-3T3 cells that were stably transfected with pBPuro-MycER^TM (for conditional c-Myc expression) or with the empty vector. The results obtained by Real Time PCR show that RECK inhibition by c-Myc is dependent on protein synthesis and chromatin remodelling.
Supported by: FAPESP, CNPq, FINEP and PRP-USP.