Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues

PGP 9.5 is a neurospecific peptide that functions to remove ubiquitin from ubiquitinated cellular proteins, thereby preventing them from targeted degr adation by the proteasome-dependent pathway or regulating their localizatio n, activity or structure. Using the serial analysis of gene expression meth od (SAGE), we initially found that the PGP9.5 transcript and protein was hi ghly expressed in more than 50% of primary lung cancers and nearly all lung cancer cell lines but was not detectable in the normal lung. This increase d expression could be the result of transcriptional regulation accompanied by methylation changes at the CpG island of the promoter region. We studied the methylation status of the cytosines at the promoter region of human PG P9.5 using sodium bisulfite genomic sequencing in normal and neoplastic cel ls. Although no methylation of PGP9.5 promoter was observed in the normal l ung, normal cervical tissue, and lung cancer cell lines, this region was de nsely methylated in the HeLa cell line. Exposure to HeLa cells to the demet hylating agent, 5-aza-2 ' -deoxycytidine, led to re-expression of PGP9.5. T his data suggested that while other mechanisms may be involved in the frequ ent overexpression of PGP9.5 gene in lung tumors and lung cancer cell lines , promoter methylation may play a role in the transcriptional suppression o f PGP9.5 gene expression in the cervical tissue-derived HeLa cell line. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.