Amplification of MUC1 in prostate cancer metastasis and CRPC development
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Nicholas Wong1,2,3, Pierre Major4, Anil Kapoor2,5, Fengxiang Wei1,2,3,6, Judy Yan1,2,3, Tariq Aziz7, Mingxing Zheng8,9, Dulitha Jayasekera1,2,3, Jean-Claude Cutz7, Mathilda Jing Chow1,2,3, Damu Tang1,2,3
1Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
2Father Sean O’Sullivan Research Institute, Hamilton, Ontario, Canada
3The Hamilton Center for Kidney Research, St. Joseph’s Hospital, Hamilton, Ontario, Canada
4Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, Ontario, Canada
5Department of Surgery, McMaster University, Hamilton, Ontario, Canada
6The Genetics Laboratory, Longgang District Maternity and Child Healthcare Hospital, Longgang District, Shenzhen, Guangdong, P.R. China
7Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
8Department of Respiratory Medicine, Shenzhen 2nd People’s Hospital, Shenzhen, Guangdong, China
9Department of Respiratory Disease, The First Affiliated Hospital of Shenzhen University Medical School, Shenzhen, Guangdong, China
Damu Tang, email: email@example.com
Keywords: MUC1, prostate cancer, prostate cancer stem cells, metastasis, castration resistant prostate cancer
Received: April 16, 2016 Accepted: October 16, 2016 Published: November 04, 2016
Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues. By analyzing MUC1 mRNA levels and gene copy number (GCN) using the OncomineTM database, elevations in MUC1 mRNA in 82 metastases versus 280 primary PCs and in MUC1 GCN in 37 metastases over 181 primary tumors were demonstrated. Analysis of genomic datasets within cBioPortal revealed increases in MUC1 GCN in 2% (6/333) of primary PCs, 6% (9/150) of metastatic PCs, and 33% (27/82) of CRPCs; in comparison, the respective increase in androgen receptor (AR) GCN was 1%, 63%, and 56%, revealing a specific increase in MUC1 GCN for CRPC. Furthermore, a 25-gene MUC1 network was amplified in 52% of CRPCs compared to 69% of CRPCs displaying increases in an AR co-regulator group. While genomic alterations in the MUC1 network largely overlap with those in the AR group, 18 CRPCs (66.7% being neuroendocrine PC) showed genomic alterations only in the MUC1 network. Moreover, genomic alterations in the MUC1 network correlated with PC relapse. Collectively, our observations suggest a combination therapy involving MUC1-based immunotherapy and androgen deprivation.
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