Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer

Rachel M Barker, Kalina M Biernacka, Georgina Kingshott, Alex Sewell, Paida Gwiti, Richard M Martin, J. Athene Lane, Lucy McGeagh, Anthony J Koupparis, Edward Rowe, Jon Oxley, Claire M Perks*, Jeff M. P. Holly

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Aims
To examine associations between the transcription factors CCCTC-binding factor (CTCF) and forkhead box protein A1 (FOXA1) and the androgen receptor (AR) and their association with components of the insulin-like growth factor (IGF)-pathway in a cohort of men with localized prostate cancer.

Methods
Using prostate tissue samples collected during the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) trial (N = 70 to 92, depending on section availability), we assessed the abundance of CTCF, FOXA1, AR, IGFIR, p-mTOR, PTEN and IGFBP-2 proteins using a modified version of the Allred scoring system. Validation studies were performed using large, publicly available datasets (TCGA) (N = 489).

Results
We identified a strong correlation between CTCF and AR staining with benign prostate tissue. CTCF also strongly associated with the IGFsingle bondIR, with PTEN and with phospho-mTOR. FOXA1 was also correlated with staining for the IGF-IR, with IGFBP-2 and with staining for activated phosphor-mTOR. The staining for the IGF-IR was strongly correlated with the AR.

Conclusion
Our findings emphasise the close and complex links between the endocrine controls, well known to play an important role in prostate cancer, and the transcription factors implicated by the recent genetic evidence.
Original languageEnglish
Article number101533
Number of pages7
JournalGrowth Hormone and IGF Research
Volume69-70
Early online date14 Apr 2023
DOIs
Publication statusPublished - 20 Apr 2023

Bibliographical note

Funding Information:
RMM is a National Institute for Health Research Senior Investigator (NIHR202411). RMM and JAL are supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM and JAL are also supported by the NIHR Bristol Biomedical Research Centre which is funded by the NIHR (BRC-1215-20011) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol . RMM is affiliated with the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4) and the University of Bristol. Department of Health and Social Care disclaimer: The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2023

Structured keywords

  • ICEP
  • ICEP2

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