ESTRO 2024 - Abstract Book

S5433

Radiobiology - Tumour biology

ESTRO 2024

ALDH1A3 gene increased the PLK3 gene and protein expression level. We next performed Chromatin immunoprecipitation (ChIP) analysis with antibodies directed against total AR and RARA proteins and revealed significantly increased precipitation of different promoter regions of PLK3 with RARA and AR antibodies compared to the control IgG. Further in vitro experiments demonstrated that PLK3 regulates PCa cell migration, proliferation and radioresistance. In vivo experiments revealed ALDH1A1 as a gene essential for the coordination of both extravasation and survival of cancer cells in contrast to ALDH1A3. ALDH1A1 regulates tumor cells homing to the bones and bone marrow colonization in a syngeneic murine PCa model. We also observed an overexpression of the ALDH1A1 gene in the bone metastatic cells, although the expression of ALDH1A3 was not significantly altered.

Conclusion:

These results suggest that PLK3 was identified as a transcriptional target oppositely regulated by ALDH1A1 and ALDH1A3 genes in RAR and AR-dependent manner. PLK3 contributes to the control of prostate cancer cell proliferation, migration, DNA repair, and radioresistance. ALDH1A1 gain in prostate cancer bone metastases is associated with high PLK3 expression.

Keywords: Prostate cancer, radioresistance, bone metastasis

References:

1. Furesi G., et al., Trends Cancer. 2021 2. Skvortsov S., et al. Stem Cells. 2018 3. Cojoc M., et al. Cancer Res. 2015 4. Polkinghorn W., et al. Cancer Discov. 2013 5. Salberg U., et al. Br J Cancer. 2022 6. Mukha A., et al. Theranostics. 2021 7. Chuang KH., Mol Endocrinol. 2005

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Digital Poster

Exploring Biological Differences in Rectal Cancer Tumours Before Neoadjuvant Chemoradiotherapy

Lily V Hillson 1 , S:CORT Consortium 2 , Ashley K McCulloch 1 , Timothy S Maughan 2 , Joanne Edwards 1 , Philip D Dunne 3,4 , Sean M O'Cathail 1 , Campbell S Roxburgh 1 1 University of Glasgow, School of Cancer Sciences, Glasgow, United Kingdom. 2 University of Oxford, Oxford Institute of Radiation Oncology, Oxford, United Kingdom. 3 Queens University Belfast, Patrick G. Johnston Centre for Cancer Research, Belfast, United Kingdom. 4 Cancer Research UK, Beatson Institute for Cancer Research, Glasgow, United Kingdom