Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types

Ian Krop, Audrey Player, Ana Tablante, Michele Taylor-Parker, Jaana Lahti-Domenici, Junya Fukuoka, Surinder Kumar Batra, Nickolas Papadopoulos, William G. Richards, David J. Sugarbaker, Renée L. Wright, Judy Shim, Thomas A. Stamey, William R. Sellers, Massimo Loda, Matthew Meyerson, Ralph Hruban, Jin Jen, Kornelia Polyak

Research output: Contribution to journalArticle

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Abstract

HIN-1 (high in normal-1) is a candidate tumor suppressor identified as a gene silenced by methylation in the majority of breast carcinomas. HIN-1 is highly expressed in the mammary gland, trachea, lung, prostate, pancreas, and salivary gland, and in the lung, its expression is primarily restricted to bronchial epithelial cells. In this report, we show that, correlating with the secretory nature of HIN-1, high levels of HIN-1 protein are detected in bronchial lavage, saliva, plasma, and serum. To determine if, similar to breast carcinomas, HIN-1 is also silenced in tumors originating from other organs with high HIN-1 expression, we analyzed its expression and promoter methylation status in lung, prostate, and pancreatic carcinomas. Nearly all prostate and a significant fraction of lung and pancreatic carcinomas showed HIN-1 hypermethylation, and the majority of lung and prostate tumors lacked HIN-1 expression. In lung carcinomas, the degree of HIN-1 methylation differed among tumor subtypes (P = 0.02), with the highest level of HIN-1 methylation observed in squamous cell carcinomas and the lowest in small cell lung cancer. In lung adenocarcinomas, the expression of HIN-1 correlated with cellular differentiation status. Hypermethylation of the HIN-1 promoter was also frequently observed in normal tissue adjacent to tumors but not in normal tissue from noncancer patients, implying that HIN-1 promoter methylation may be a marker of premalignant changes. Thus, silencing of HIN-1 expression and methylation of its promoter occurs in multiple human cancer types, suggesting that elimination of HIN-1 function may contribute to several forms of epithelial tumorigenesis.

Original languageEnglish (US)
Pages (from-to)489-494
Number of pages6
JournalMolecular Cancer Research
Volume2
Issue number9
StatePublished - Sep 1 2004

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Methylation
Lung
Prostate
Neoplasms
Breast Neoplasms
Small Cell Lung Carcinoma
Bronchoalveolar Lavage
Human Mammary Glands
Trachea
Salivary Glands
Saliva
Pancreas
Squamous Cell Carcinoma
Carcinogenesis
Epithelial Cells
Carcinoma
Serum
Genes
Proteins
Pancreatic Carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Krop, I., Player, A., Tablante, A., Taylor-Parker, M., Lahti-Domenici, J., Fukuoka, J., ... Polyak, K. (2004). Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Molecular Cancer Research, 2(9), 489-494.

Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. / Krop, Ian; Player, Audrey; Tablante, Ana; Taylor-Parker, Michele; Lahti-Domenici, Jaana; Fukuoka, Junya; Batra, Surinder Kumar; Papadopoulos, Nickolas; Richards, William G.; Sugarbaker, David J.; Wright, Renée L.; Shim, Judy; Stamey, Thomas A.; Sellers, William R.; Loda, Massimo; Meyerson, Matthew; Hruban, Ralph; Jen, Jin; Polyak, Kornelia.

In: Molecular Cancer Research, Vol. 2, No. 9, 01.09.2004, p. 489-494.

Research output: Contribution to journalArticle

Krop, I, Player, A, Tablante, A, Taylor-Parker, M, Lahti-Domenici, J, Fukuoka, J, Batra, SK, Papadopoulos, N, Richards, WG, Sugarbaker, DJ, Wright, RL, Shim, J, Stamey, TA, Sellers, WR, Loda, M, Meyerson, M, Hruban, R, Jen, J & Polyak, K 2004, 'Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types', Molecular Cancer Research, vol. 2, no. 9, pp. 489-494.
Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J et al. Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Molecular Cancer Research. 2004 Sep 1;2(9):489-494.
Krop, Ian ; Player, Audrey ; Tablante, Ana ; Taylor-Parker, Michele ; Lahti-Domenici, Jaana ; Fukuoka, Junya ; Batra, Surinder Kumar ; Papadopoulos, Nickolas ; Richards, William G. ; Sugarbaker, David J. ; Wright, Renée L. ; Shim, Judy ; Stamey, Thomas A. ; Sellers, William R. ; Loda, Massimo ; Meyerson, Matthew ; Hruban, Ralph ; Jen, Jin ; Polyak, Kornelia. / Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. In: Molecular Cancer Research. 2004 ; Vol. 2, No. 9. pp. 489-494.
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