Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids.

Abstract

The ectopic ACTH syndrome is caused by abnormal expression of the POMC gene product arising from non-pituitary tumors in response to the ectopic activation of the pituitary-specific promoter of this gene. It has been proved that methylation of the CpG island in the promoter region is associated with silencing of some genes. Using bisulphite sequencing, we identified hypermethylation in the 5' promoter region of the POMC gene in three normal thymuses and one large cell lung cancer, and hypomethylation in five thymic carcinoid tumors resected from patients with ectopic ACTH syndrome. The region undergoing hypermethylation was narrowed to coordinates -417 to -260 of the POMC promoter. Furthermore, we observed that the levels of POMC expression correlated with the methylation density at -417 to -260 bp across the E2 transcription factor binding region of the POMC promoter. It is concluded that hypomethylation of the POMC promoter in thymic carcinoids correlates with POMC overexpression and the ectopic ACTH syndrome.

• Authors: Lei Ye, Xiaoying Li, Xiangyin Kong, Weiqing Wang, Yufang Bi, Landian Hu, Bin Cui, Xi Li, Guang Ning
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 185 Issue 2 Pg. 337-43 (May 2005) ISSN: 0022-0795 [Print] England
• PMID: 15845926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Pro-Opiomelanocortin

Topics

• ACTH Syndrome, Ectopic (metabolism)
• Carcinoid Tumor (metabolism)
• CpG Islands
• DNA Methylation
• Gene Expression
• Humans
• Immunohistochemistry (methods)
• Pro-Opiomelanocortin (genetics)
• Promoter Regions, Genetic
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Thymus Neoplasms (metabolism)