The Histone Acetyltransferase GCN5 Expression Is Elevated and Regulated by c-Myc and E2F1 Transcription Factors in Human Colon Cancer.

Abstract

The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

• Authors: Yan-Wei Yin, Hong-Jian Jin, Wenjing Zhao, Beixue Gao, Jiangao Fang, Junmin Wei, Donna D Zhang, Jianing Zhang, Deyu Fang
• Journal: Gene expression (Gene Expr) Vol. 16 Issue 4 Pg. 187-96 ( 2015) ISSN: 1052-2166 [Print] United States
• PMID: 26637399 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• E2F1 Transcription Factor
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• p300-CBP Transcription Factors
• p300-CBP-associated factor

Topics

• Colonic Neoplasms (enzymology, metabolism, pathology)
• E2F1 Transcription Factor (physiology)
• Humans
• Infant
• Proto-Oncogene Proteins c-myc (physiology)
• RNA, Messenger (genetics)
• p300-CBP Transcription Factors (genetics, metabolism)