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

doi:10.1016/j.ghir.2023.101533

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 journal › Article (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 language	English
Article number	101533
Number of pages	7
Journal	Growth Hormone and IGF Research
Volume	69-70
Early online date	14 Apr 2023
DOIs	https://doi.org/10.1016/j.ghir.2023.101533
Publication status	Published - 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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.ghir.2023.101533

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Barker, R. M., Biernacka, K. M., Kingshott, G., Sewell, A., Gwiti, P., Martin, R. M., Lane, J. A., McGeagh, L., Koupparis, A. J., Rowe, E., Oxley, J., Perks, C. M., & Holly, J. M. P. (2023). Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer. Growth Hormone and IGF Research, 69-70, Article 101533. https://doi.org/10.1016/j.ghir.2023.101533

@article{061b27e48c8441e2b3abb360a2741546,

title = "Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer",

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.",

author = "Barker, \{Rachel M\} and Biernacka, \{Kalina M\} and Georgina Kingshott and Alex Sewell and Paida Gwiti and Martin, \{Richard M\} and Lane, \{J. Athene\} and Lucy McGeagh and Koupparis, \{Anthony J\} and Edward Rowe and Jon Oxley and Perks, \{Claire M\} and Holly, \{Jeff M. P.\}",

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: {\textcopyright} 2023",

year = "2023",

month = apr,

day = "20",

doi = "10.1016/j.ghir.2023.101533",

language = "English",

volume = "69-70",

journal = "Growth Hormone and IGF Research",

issn = "1096-6374",

publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer

AU - Barker, Rachel M

AU - Biernacka, Kalina M

AU - Kingshott, Georgina

AU - Sewell, Alex

AU - Gwiti, Paida

AU - Martin, Richard M

AU - Lane, J. Athene

AU - McGeagh, Lucy

AU - Koupparis, Anthony J

AU - Rowe, Edward

AU - Oxley, Jon

AU - Perks, Claire M

AU - Holly, Jeff M. P.

N1 - 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

PY - 2023/4/20

Y1 - 2023/4/20

N2 - 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.

AB - 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.

UR - https://www.sciencedirect.com/science/article/abs/pii/S1096637423000114?via%3Dihub

U2 - 10.1016/j.ghir.2023.101533

DO - 10.1016/j.ghir.2023.101533

M3 - Article (Academic Journal)

C2 - 37086646

SN - 1096-6374

VL - 69-70

JO - Growth Hormone and IGF Research

JF - Growth Hormone and IGF Research

M1 - 101533

ER -

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

Abstract

Bibliographical note

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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

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

Abstract

Bibliographical note

UN SDGs

Research Groups and Themes

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this