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

Oncogene
Martin L ReadC J McCabe

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). Consistent with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean genetic instability (GI) index of 35.8±2.6%, as well as significant induction of gross chromosomal aberrations in thyroidal TPC-1 cells following overexpression of PBF and PTTG. We extended our findings to human thyroid cancer using TCGA data sets (n=322) and found striking correlations with PBF and PTTG expression in well-characterised DDR gene panel RNA-seq data. In addition, geneti...Continue Reading

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Citations

Sep 22, 2017·Journal of Molecular Endocrinology·Marika H TesselaarTheo S Plantinga
Jan 4, 2020·Oncology Letters·Jin-Zhu LuoLing-Jie Zhang
Oct 30, 2020·Cancer Management and Research·Shengnan WangJianjun Dong

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Methods Mentioned

BETA
2 hybrid
transgenic
PCR
chromosomal aberrations
RNA-seq
ubiquitination
RNAseq

Software Mentioned

Finder
ImageJ
DOTS
DAVID
Excel
Peak Scanner
SPSS Statistics
Photoshop

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