The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines

Mark L Gonzalgo, Toshiro Hayashida, Christina M. Bender, Martha M. Pao, Yvonne C. Tsai, Felicidad A. Gonzales, Hung D. Nguyen, TuDung T. Nguyen, Peter A. Jones

Research output: Contribution to journalArticle

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Abstract

Methylation of CpG sites in the control regions of tumor suppressor genes may be an important mechanism for their heritable, yet reversible, transcriptional inactivation. These changes in methylation may impair the proper expression and/or function of cell cycle regulatory genes and confer a selective growth advantage to affected cells. Detailed methylation analysis using genomic bisulfite sequencing was performed on a series of subclones of a bladder cancer cell line in which a hypermethylated p16 gene had been reactivated by transient treatment with 5-aza-2'-deoxycytidine. Methylation of the CpG island in the promoter of the p16 gene in human bladder cancer cells did not stop the formation of a transcript initiated 20 kb upstream by the p19 promoter but did prevent the expression of a p16 transcript. Furthermore, we show that reactivant clones that expressed p16 at varying levels contained heterogeneous methylation patterns, suggesting that p16 expression can occur even in the presence of a relatively heavily methylated coding region. We also present the first functional evidence that methylation of only a small number of CpG sites can significantly down-regulate p16 promoter activity, thus providing support for the model of progressive inactivation of this tumor suppressor gene by DNA methylation.

Original languageEnglish (US)
Pages (from-to)1245-1252
Number of pages8
JournalCancer Research
Volume58
Issue number6
StatePublished - Mar 15 1998
Externally publishedYes

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DNA Methylation
Urinary Bladder Neoplasms
Methylation
Cell Line
p16 Genes
decitabine
Tumor Suppressor Genes
cdc Genes
CpG Islands
Regulator Genes
Down-Regulation
Clone Cells
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gonzalgo, M. L., Hayashida, T., Bender, C. M., Pao, M. M., Tsai, Y. C., Gonzales, F. A., ... Jones, P. A. (1998). The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Research, 58(6), 1245-1252.

The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. / Gonzalgo, Mark L; Hayashida, Toshiro; Bender, Christina M.; Pao, Martha M.; Tsai, Yvonne C.; Gonzales, Felicidad A.; Nguyen, Hung D.; Nguyen, TuDung T.; Jones, Peter A.

In: Cancer Research, Vol. 58, No. 6, 15.03.1998, p. 1245-1252.

Research output: Contribution to journalArticle

Gonzalgo, ML, Hayashida, T, Bender, CM, Pao, MM, Tsai, YC, Gonzales, FA, Nguyen, HD, Nguyen, TT & Jones, PA 1998, 'The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines', Cancer Research, vol. 58, no. 6, pp. 1245-1252.
Gonzalgo ML, Hayashida T, Bender CM, Pao MM, Tsai YC, Gonzales FA et al. The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. Cancer Research. 1998 Mar 15;58(6):1245-1252.
Gonzalgo, Mark L ; Hayashida, Toshiro ; Bender, Christina M. ; Pao, Martha M. ; Tsai, Yvonne C. ; Gonzales, Felicidad A. ; Nguyen, Hung D. ; Nguyen, TuDung T. ; Jones, Peter A. / The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines. In: Cancer Research. 1998 ; Vol. 58, No. 6. pp. 1245-1252.
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