Journal Article

Frequent silencing of <i>protocadherin 17</i>, a candidate tumour suppressor for esophageal squamous cell carcinoma

Shigeo Haruki, Issei Imoto, Ken-ichi Kozaki, Takeshi Matsui, Hiroshi Kawachi, Shuhei Komatsu, Tomoki Muramatsu, Yutaka Shimada, Tatsuyuki Kawano and Johji Inazawa

in Carcinogenesis

Volume 31, issue 6, pages 1027-1036
Published in print June 2010 | ISSN: 0143-3334
Published online March 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq053
Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous cell carcinoma

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Protocadherins are a subfamily of the cadherin superfamily, but little is known about their functions. We identified a homozygous loss of protocadherin (PCDH) 17 in the course of a program to screen a panel of esophageal squamous cell carcinoma (ESCC) cell lines for genomic copy number aberrations. PCDH17 messenger RNA was expressed in normal esophageal tissue but not in the majority of ESCC cell lines without a homozygous deletion of this gene and restored in gene-silenced ESCC cells after treatment with 5-aza-2′-deoxycytidine. The DNA methylation status of the PCDH17 CpG island correlated inversely with the PCDH17 expression, and a putative methylation target region showed promoter activity. The methylation of the PCDH17 promoter was also associated with the silencing of gene expression in primary ESCC partly. Among primary ESCC cases, the silencing of PCDH17 protein expression was associated with a poorer differentiation status of ESCC cells and possibly with prognosis in a subset of this tumour. Restoration of PCDH17 expression in ESCC cells reduced cell proliferation and migration/invasion. These results suggest that silencing of PCDH17 expression through hypermethylation of the promoter or other mechanisms leads to loss of its tumour-suppressive activity, which may be a factor in the carcinogenesis of a subgroup of ESCCs.

Journal Article.  7315 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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