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

Siane Lopes Bittencourt Rosas, Otavia Luisa Caballero, Seung Myung Dong, Mariada Gloriada Costa Carvalho, David Sidransky, Jin Jen

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


PGP 9.5 is a neurospecific peptide that functions to remove ubiquitin from ubiquitinated cellular proteins, thereby preventing them from targeted degradation by the proteasome-dependent pathway or regulating their localization, activity or structure. Using the serial analysis of gene expression method (SAGE), we initially found that the PGP9.5 transcript and protein was highly 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 increased 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 PGP9.5 using sodium bisulfite genomic sequencing in normal and neoplastic cells. Although no methylation of PGP9.5 promoter was observed in the normal lung, normal cervical tissue, and lung cancer cell lines, this region was densely methylated in the HeLa cell line. Exposure to HeLa cells to the demethylating agent, 5-aza-2′-deoxycytidine, led to re-expression of PGP9.5. This data suggested that while other mechanisms may be involved in the frequent overexpression of PGP9.5 gene in lung tumors and lung cancer cell lines, promoter methylation may play a role in the transcriptional suppression of PGP9.5 gene expression in the cervical tissue-derived HeLa cell line.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalCancer Letters
Issue number1
StatePublished - Sep 10 2001


  • HeLa cell
  • Lung cancer cell line
  • Methylation
  • PGP9.5
  • Promoter

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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