Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer

Breast Cancer Research : BCR
Azlena AliMarie McIlroy

Abstract

HOX genes play vital roles in growth and development, however, atypical redeployment of these genes is often associated with steroidal adaptability in endocrine cancers. We previously identified HOXC11 to be an indicator of poor response to hormonal therapy in breast cancer. In this study we aimed to elucidate genes regulated by HOXC11 in the endocrine resistant setting. RNA-sequencing paired with transcription factor motif-mapping was utilised to identify putative HOXC11 target genes in endocrine resistant breast cancer. Validation and functional evaluation of the target gene, prosaposin (PSAP), was performed in a panel of endocrine sensitive and resistant breast cancer cell lines. The clinical significance of this finding was explored in clinical cohorts at both mRNA and protein level. PSAP was shown to be regulated by HOXC11 in both tamoxifen and aromatase inhibitor (AI) resistant cell lines. Transcript levels of HOXC11 and PSAP correlated strongly in samples of primary breast tumours (r = 0.7692, n = 51). PSAP has previously been reported to activate androgen receptor (AR) in prostate cancer cells. In a panel of breast cancer cell lines it was shown that endocrine resistant cells exhibit innately elevated levels of AR compa...Continue Reading

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Citations

Mar 14, 2018·Endocrine-related Cancer·Tiago Vieira AugustoCristina Amaral
Dec 18, 2018·Endocrine-related Cancer·KeeMing ChiaElgene Lim
May 22, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·David A PattenRichard B Richardson
Sep 15, 2017·Cancer Investigation·S E SeminaM A Krasil'nikov
May 22, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel BleachMarie McIlroy

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Methods Mentioned

BETA
RNA-seq
transfections
reverse transcription PCR
immunoprecipitation
nuclear translocation
ChIP
ELISA

Software Mentioned

TFFind
Cufflinks
FIMO
Graphpad Prism
ImageJ
CellSens Olympus
Tophat
CellSens Entry
Image J
Cuffdiff

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