@Article{096504019X15555794826018,
AUTHOR = {Annemarie E. M. Post, Johan Bussink, Fred C. G. J. Sweep, Paul N. Span},
TITLE = {Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene  Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {1},
PAGES = {33--40},
URL = {http://www.techscience.com/or/v28n1/48545},
ISSN = {1555-3906},
ABSTRACT = {Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that 
DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence 
of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression 
of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that 
were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic 
for several DNA damage repair pathways was investigated, as well as expression of genes involved in different 
phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was 
assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential 
gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were 
more than two times upregulated (<i>NEIL1 </i>and <i>EME2</i>), and three DNA damage repair genes were more than two 
times downregulated (<i>PCNA</i>, <i>BRIP1</i>, and <i>BARD1</i>). However, these were not associated with outcome after 
radiotherapy in the TCGA breast cancer cohort. Genes involved in G<sub>1</sub>, G<sub>1</sub>/S, G<sub>2</sub>, and G<sub>2</sub>/M phases were lower 
expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two 
times upregulated (<i>MAPK13</i>) or downregulated (<i>E2F2</i>, <i>CKS2</i>, <i>GINS2</i>, <i>PCNA</i>, <i>MCM5</i>, and <i>EIF5A2</i>) were not 
associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA 
damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in 
both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these 
cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.},
DOI = {10.3727/096504019X15555794826018}
}