Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas

K. O. Toyooka, S. Toyooka, A. K. Virmani, U. G. Sathyanarayana, D. M. Euhus, M. Gilcrease, J. D. Minna, A. F. Gazdar

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5′-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.

Original languageEnglish (US)
Pages (from-to)4556-4560
Number of pages5
JournalCancer Research
Volume61
Issue number11
StatePublished - Jun 1 2001

Fingerprint

Methylation
Breast Neoplasms
Lung
Genes
Cell Line
Lung Neoplasms
decitabine
Tumor Suppressor Genes
Neoplasms
Gene Expression
Polymerase Chain Reaction
Chromosomes, Human, Pair 3
Small Cell Lung Carcinoma
Cadherins
Tumor Cell Line
Genetic Promoter Regions
Non-Small Cell Lung Carcinoma
Reverse Transcription
H-cadherin
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Toyooka, K. O., Toyooka, S., Virmani, A. K., Sathyanarayana, U. G., Euhus, D. M., Gilcrease, M., ... Gazdar, A. F. (2001). Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Research, 61(11), 4556-4560.

Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. / Toyooka, K. O.; Toyooka, S.; Virmani, A. K.; Sathyanarayana, U. G.; Euhus, D. M.; Gilcrease, M.; Minna, J. D.; Gazdar, A. F.

In: Cancer Research, Vol. 61, No. 11, 01.06.2001, p. 4556-4560.

Research output: Contribution to journalArticle

Toyooka, KO, Toyooka, S, Virmani, AK, Sathyanarayana, UG, Euhus, DM, Gilcrease, M, Minna, JD & Gazdar, AF 2001, 'Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas', Cancer Research, vol. 61, no. 11, pp. 4556-4560.
Toyooka KO, Toyooka S, Virmani AK, Sathyanarayana UG, Euhus DM, Gilcrease M et al. Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Research. 2001 Jun 1;61(11):4556-4560.
Toyooka, K. O. ; Toyooka, S. ; Virmani, A. K. ; Sathyanarayana, U. G. ; Euhus, D. M. ; Gilcrease, M. ; Minna, J. D. ; Gazdar, A. F. / Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. In: Cancer Research. 2001 ; Vol. 61, No. 11. pp. 4556-4560.
@article{900a734ceb2a4b19b15d5945997d730d,
title = "Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas",
abstract = "Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33{\%}) and cell lines (7 of 20, 35{\%}). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43{\%}) and cell lines (15 of 30, 50{\%}) than in small cell lung cancer cell lines (6 of 30, 20{\%}; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91{\%}) tumor cell lines. CDH13 expression was present in 24 of 30 (80{\%}) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5′-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.",
author = "Toyooka, {K. O.} and S. Toyooka and Virmani, {A. K.} and Sathyanarayana, {U. G.} and Euhus, {D. M.} and M. Gilcrease and Minna, {J. D.} and Gazdar, {A. F.}",
year = "2001",
month = "6",
day = "1",
language = "English (US)",
volume = "61",
pages = "4556--4560",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas

AU - Toyooka, K. O.

AU - Toyooka, S.

AU - Virmani, A. K.

AU - Sathyanarayana, U. G.

AU - Euhus, D. M.

AU - Gilcrease, M.

AU - Minna, J. D.

AU - Gazdar, A. F.

PY - 2001/6/1

Y1 - 2001/6/1

N2 - Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5′-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.

AB - Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5′-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=0035360824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035360824&partnerID=8YFLogxK

M3 - Article

VL - 61

SP - 4556

EP - 4560

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 11

ER -