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Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1
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Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1
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Journal Article
Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1
2020
Overview
Emerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we evaluated the association of p-S6K1 expression with radio-resistance in breast cancer cell lines and patients. During median follow-up of 33 (range, 0.1–111) months for 1770 primary breast cancer patients who underwent surgery, patients expressing p-S6K1 showed worse 10-year loco-regional recurrence-free survival (LRFS) compared to that of p-S6K1-negative patients after radiotherapy (93.4% vs. 97.7%,
p
= 0.015). Multivariate analysis revealed p-S6K1 expression as a predictor of radio-resistance (hazard ratio 7.9, 95% confidence interval 1.1–58.5,
p
= 0.04).
In vitro
, CD44
high
/CD24
low
MCF7 cells with a radioresistant phenotype expressed higher levels of p-S6K1 than control MCF7 cells. Furthermore, the combination of radiation with treatment of everolimus, an mTOR-S6K1 pathway inhibitor, sensitised CD44
high
/CD24
low
MCF7 cells to a greater extent than MCF7 cells. This study provides
in vivo
and
in vitro
evidence for p-S6K1 expression status as an important marker for predicting the resistance to radiotherapy and as a possible target for radio-sensitization in breast cancer patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/100
/ 14/63
/ 82
/ 82/51
/ 82/80
/ Breast Neoplasms - radiotherapy
/ Female
/ Humanities and Social Sciences
/ Humans
/ Patients
/ Radiation Tolerance - genetics
/ Ribosomal Protein S6 Kinases, 70-kDa - genetics
/ Ribosomal Protein S6 Kinases, 70-kDa - metabolism
/ Science
/ Signal Transduction - genetics
/ Surgery
