TY - JOUR
T1 - Promoter methylation of HIN-1 in the progression to esophageal squamous cancer.
AU - Guo, Mingzhou
AU - Ren, Jingli
AU - Brock, Malcolm V.
AU - Herman, James G.
AU - Carraway, Hetty E.
N1 - Funding Information:
We would like to thank the grant support from the Flight Attendant Medical Research Institute (FAMRI) (number 32053) and the NCI (Early Detection Research Network) CA-84986. We would also like to personally thank Amanda Blackford for her assistance with statistical analysis.
Copyright:
This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PY - 2008/11
Y1 - 2008/11
N2 - HIN-1 (High in normal-1) is a tumor suppressor gene that is highly expressed in many epithelial tissues, including breast lung, trachea, pancreas, prostrate and salivary gland. Inactivation of HIN-1 expression by promoter methylation is frequent in many epithelial carcinomas and carcinoma-in-situ, including breast, lung and nasopharyngeal. Because HIN-1 silencing commences at an early stage of malignant transformation in these tissues, it may be a useful marker for tumor presence. The status of HIN-1 regulation in esophageal cancer has not been previously reported. Thus, we analyzed 18 esophageal cancer cell lines for HIN-1 expression and methylation by reverse transcription PCR (RT-PCR) and methylation specific PCR (MSP). HIN-1 gene silencing and promoter methylation was present in 13 (72%) of the cell lines. Bisulfite-treated sequencing confirmed the methylation status in cell lines and demonstrated dense methylation of HIN-1 throughout the promoter region. Epigenetic changes of HIN-1 were examined throughout the progression of carcinogenesis in esophageal squamous lesions through analysis of archived surgical specimens from patients with normal esophageal mucosa (n = 17), grade I dysplasia (n = 39), grade II dysplasia (n = 12), grade III dysplasia (n = 9), and invasive squamous esophageal cancer (n = 126). Methylation of HIN-1 was present in 0% of normal mucosa, 31% of grade I dysplasia, 33% of grade II dysplasia, 44% of grade III dysplasia, and 50% of esophageal cancer specimens analyzed. These studies demonstrate HIN-1 silencing is associated with dense promoter region hypermethylation in esophageal cancer and suggest that methylation of HIN-1 is an early event in dysplastic transformation.
AB - HIN-1 (High in normal-1) is a tumor suppressor gene that is highly expressed in many epithelial tissues, including breast lung, trachea, pancreas, prostrate and salivary gland. Inactivation of HIN-1 expression by promoter methylation is frequent in many epithelial carcinomas and carcinoma-in-situ, including breast, lung and nasopharyngeal. Because HIN-1 silencing commences at an early stage of malignant transformation in these tissues, it may be a useful marker for tumor presence. The status of HIN-1 regulation in esophageal cancer has not been previously reported. Thus, we analyzed 18 esophageal cancer cell lines for HIN-1 expression and methylation by reverse transcription PCR (RT-PCR) and methylation specific PCR (MSP). HIN-1 gene silencing and promoter methylation was present in 13 (72%) of the cell lines. Bisulfite-treated sequencing confirmed the methylation status in cell lines and demonstrated dense methylation of HIN-1 throughout the promoter region. Epigenetic changes of HIN-1 were examined throughout the progression of carcinogenesis in esophageal squamous lesions through analysis of archived surgical specimens from patients with normal esophageal mucosa (n = 17), grade I dysplasia (n = 39), grade II dysplasia (n = 12), grade III dysplasia (n = 9), and invasive squamous esophageal cancer (n = 126). Methylation of HIN-1 was present in 0% of normal mucosa, 31% of grade I dysplasia, 33% of grade II dysplasia, 44% of grade III dysplasia, and 50% of esophageal cancer specimens analyzed. These studies demonstrate HIN-1 silencing is associated with dense promoter region hypermethylation in esophageal cancer and suggest that methylation of HIN-1 is an early event in dysplastic transformation.
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U2 - 10.4161/epi.3.6.7158
DO - 10.4161/epi.3.6.7158
M3 - Article
C2 - 19098448
AN - SCOPUS:63849230673
VL - 3
SP - 336
EP - 341
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 6
ER -