Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Cocktail & Poster Display session

22P - Emerging role of histone acetyltransferase CBP in breast cancer cells undergoing DNA damage


06 Mar 2023


Cocktail & Poster Display session


Wafaa Ramadan


Annals of Oncology (2023) 8 (1suppl_2): 100901-100901. 10.1016/esmoop/esmoop100901


W.S. Ramadan1, S. Ahmed2, L. Lozon1, S. Mouffak1, W. Mansour3, R. El-Awady4

Author affiliations

  • 1 Research Institute For Medical And Health Sciences, University of Sharjah, 27272 - Sharjah/AE
  • 2 Department Of Biosciences And Chemistry, Sheffield Hallam University, S1 1WB - Sheffield/GB
  • 3 Department Of Radiotherapy And Radio-oncology, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 - Hamburg/DE
  • 4 College Of Pharmacy, University of Sharjah, 27272 - Sharjah/AE


This content is available to ESMO members and event participants.

Abstract 22P


DNA damage response and repair defects resulted from genetic and epigenetic alterations are frequently observed among breast cancer patients and eventually affect their response to chemo- and radiotherapies. Among the epigenetic alterations, the histone acetyltransferase CREB-binding protein (CBP) was found to be dysregulated in breast cancer cells. Despite of many reports that demonstrated the role of CBP in DNA damage repair, the involvement of CBP in the initial events of activating DNA damage response pathways and the potential of targeting CBP in breast cancer therapy remains poorly understood. Here we set out to explore the role of CBP in DNA damage response in breast cancer and normal cells.


Cancer and normal breast cell lines were used to examine the expression, stability, and activity of CBP and its interaction with other proteins after DNA damage induction by chemotherapeutic agent or radiation. In addition, immunofluorescence, western blot, comet assay, colony formation assay and proximity ligation assay were performed after CBP inhibition or downregulation under DNA damage.


Our results showed that CBP is stabilized and recruited at the sites of DNA double strand breaks. The depletion of CBP impaired the DNA repair capacity and subsequently increased the sensitivity of breast cancer cells to chemo- and radiotherapy, without influencing the behavior of normal cells. Mechanistically, CBP was found to form a stable complex with ATM, a central regulator of DNA damage response, after treatment with DNA damaging agent. Furthermore, CBP depletion or inhibition impaired the autophosphorylation of ATM in breast cancer cells, suggesting it’s pivotal role in ATM activation. The impact of CBP on ATM's kinase activity was further augmented by the observed reduction in the phosphorylation of downstream proteins including Chk2, Chk1 and p53 in CBP-depleted cells. Interestingly, CBP downregulation did not interfere with the activation of ATM in non-cancerous breast cells.


Our data highlights the functional role of CBP in the response of breast cancer cells to DNA damage, particularly in ATM activation. Our results suggest that CBP could be a useful target to modulate the cellular response to DNA damaging agents in breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


This work is financially supported by grant from the King Hussein Award for Cancer Research (grant number 2021-KHA-001).


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.