TY - JOUR
T1 - Methylation status in the promoter region of the human PGP9.5 gene in cancer and normal tissues
AU - Bittencourt Rosas, Siane Lopes
AU - Caballero, Otavia Luisa
AU - Dong, Seung Myung
AU - Carvalho, Mariada Gloriada Costa
AU - Sidransky, David
AU - Jen, Jin
N1 - Funding Information:
We thank Dr James G. Herman for assisting in designing the MSP primers used in this study. This work was supported by NIH Lung SPORE grant CA58184.
PY - 2001/9/10
Y1 - 2001/9/10
N2 - 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.
AB - 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.
KW - HeLa cell
KW - Lung cancer cell line
KW - Methylation
KW - PGP9.5
KW - Promoter
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U2 - 10.1016/S0304-3835(01)00449-9
DO - 10.1016/S0304-3835(01)00449-9
M3 - Article
C2 - 11448537
AN - SCOPUS:0035840442
SN - 0304-3835
VL - 170
SP - 73
EP - 79
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -