Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Rodriguez Paredes, M (Author) Other; de Paz, AM (Author) Other; Simo Riudalbas, L (Author) Other; Sayols, S (Author) Other; Moutinho, C (Author) Other; Moran, S (Author) Other; Villanueva, A (Author) Other; Vazquez Cedeira, M (Author) Other; Lazo, PA (Author) Other; Carneiro F (Author) FMUP; Moura, CS (Author) Other; Vieira, J (Author) Other; Manuel R Teixeira (Author) ICBAS; Esteller, M (Author) Other

Journal

Title: Oncogene

Vol. 33

Pages: 2807-2813

ISSN: 0950-9232

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 103 Citations

Scopus - 110 Citations

Other information

Authenticus ID: P-008-Q0R

DOI: 10.1038/onc.2013.239

Abstract (EN): Disruption of the histone modification patterns is one of the most common features of human tumors. However, few genetic alterations in the histone modifier genes have been described in tumorigenesis. Herein we show that the histone methyltransferase SETDB1 undergoes gene amplification in non-small and small lung cancer cell lines and primary tumors. The existence of additional copies of the SETDB1 gene in these transformed cells is associated with higher levels of the corresponding mRNA and protein. From a functional standpoint, the depletion of SETDB1 expression in amplified cells reduces cancer growth in cell culture and nude mice models, whereas its overexpression increases the tumor invasiveness. The increased gene dosage of SETDB1 is also associated with enhanced sensitivity to the growth inhibitory effect mediated by the SETDB1-interfering drug mithramycin. Overall, the findings identify SETDB1 as a bona fide oncogene undergoing gene amplification-associated activation in lung cancer and suggest its potential for new therapeutic strategies.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7