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, MariadaGloriadaCosta D G D C Carvalho, David Sidransky, Jin Jen

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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
Volume170
Issue number1
DOIs
StatePublished - Sep 10 2001
Externally publishedYes

Fingerprint

Neoplasm Genes
Genetic Promoter Regions
Methylation
Lung Neoplasms
Cell Line
HeLa Cells
decitabine
Lung
Ubiquitinated Proteins
Gene Expression
CpG Islands
Cytosine
Proteasome Endopeptidase Complex
Ubiquitin
Uterine Cervical Neoplasms
Peptides
Genes
Neoplasms
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Bittencourt Rosas, S. L., Caballero, O. L., Dong, S. M., Carvalho, M. D. G. D. C., Sidransky, D., & Jen, J. (2001). Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues. Cancer Letters, 170(1), 73-79. https://doi.org/10.1016/S0304-3835(01)00449-9

Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues. / Bittencourt Rosas, Siane Lopes; Caballero, Otavia Luisa; Dong, Seung Myung; Carvalho, MariadaGloriadaCosta D G D C; Sidransky, David; Jen, Jin.

In: Cancer Letters, Vol. 170, No. 1, 10.09.2001, p. 73-79.

Research output: Contribution to journalArticle

Bittencourt Rosas, SL, Caballero, OL, Dong, SM, Carvalho, MDGDC, Sidransky, D & Jen, J 2001, 'Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues', Cancer Letters, vol. 170, no. 1, pp. 73-79. https://doi.org/10.1016/S0304-3835(01)00449-9
Bittencourt Rosas SL, Caballero OL, Dong SM, Carvalho MDGDC, Sidransky D, Jen J. Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues. Cancer Letters. 2001 Sep 10;170(1):73-79. https://doi.org/10.1016/S0304-3835(01)00449-9
Bittencourt Rosas, Siane Lopes ; Caballero, Otavia Luisa ; Dong, Seung Myung ; Carvalho, MariadaGloriadaCosta D G D C ; Sidransky, David ; Jen, Jin. / Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues. In: Cancer Letters. 2001 ; Vol. 170, No. 1. pp. 73-79.
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