Endocrine Abstracts

The androgen receptor (AR) is a major therapeutic target once prostate cancer has progressed. Even invasive cells remain initially responsive to androgen deprivation therapy (ADT) but ultimately become ADT-recurrent, which is lethal. Aggressive ADT-recurrent cells nonetheless retain active AR signaling, but in a distorted form as a result of the actions of transcription factor co-regulators, including the corepressors, for example as revealed by the TCGA consortium. We have ex...

Over the last 25 years roles have been established for vitamin D receptor (VDR) to influence cell proliferation and differentiation. For example murine knockout approaches have revealed a role for the VDR to govern mammary gland growth and function. These actions appear widespread as the enzymes responsible for 1α25(OH)2D3 generation and degradation, and the VDR itself, are all functionally present in a wide range of epithelial and haematopoietic cel...

The retinoic acid receptor gamma (RARg, encoded by NR1B3/RARG) is significantly downregulated but not mutated in the MSKCC and PRAD prostate cancer (PCa) cohorts in the Cancer Genome Atlas (TCGA) data. We investigated the consequences of modifying RARg expression.Independent of ligand, stable RARg knockdown stimulated RWPE-1 and LNCaP cells proliferation, changed the cell cycle profile and significantly altered global gene expression patterns th...

The corepressor NCOR2/SMRT regulates multiple nuclear receptors (NRs) and other transcription factors. Disruption to these functions are implicated in prostate cancer (PCa) progression but the details remain enigmatic. Therefore we sought to define the global functions of NCOR2/SMRT using isogenic PCa cell models, PCa mouse models and human PCa cohorts.We mapped the NCOR2 dependent transcriptome (RNA-seq), miRnome (miRNA-seq), methylome (EPIC methylation...

PBF is a multifunctional proto-oncogene overexpressed in thyroid and other endocrine cancers. Previously we identified a functional interaction between PBF and the tumour suppressor p53 in well-differentiated thyroid cancer (WDTC). Here, we delineate the oncogenic mechanisms of PBF, along with its binding partner PTTG, in head and neck cancer (HNSCC), in which TP53 mutations (mutTP53) are common (>50%). HNSCC tissue revealed significant upregulation of PBF and PTTG mRNA (&...