Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.

ABSTRACT: The proto-oncogene PTTG and its binding partner PBF have been widely studied in multiple cancer types, particularly thyroid and colorectal, but their combined role in tumourigenesis is uncharacterised. Here, we show for the first time that together PTTG and PBF significantly modulate DNA damage response (DDR) genes, including p53 target genes, required to maintain genomic integrity in thyroid cells. Critically, DDR genes were extensively repressed in primary thyrocytes from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG overexpression. Irradiation exposure to amplify p53 levels further induced significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 × 10^-4) compared with either PBF- (P=1.5 × 10^-3) or PTTG-expressing thyrocytes (P=NS). Consi

SUBMITTER: Read ML 

PROVIDER: S-EPMC5563453 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature