Amplification of MUC1 in prostate cancer metastasis and CRPC development
| Autor: | Mathilda Jing Chow, Nicholas Wong, Judy Yan, Anil Kapoor, Tariq Aziz, Jean-Claude Cutz, Damu Tang, Mingxing Zheng, Dulitha Jayasekera, Fengxiang Wei, Pierre Major |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology Time Factors castration resistant prostate cancer Gene Dosage Docetaxel Mice SCID Metastasis Prostate cancer 0302 clinical medicine Cell Movement Mice Inbred NOD Databases Genetic Gene Regulatory Networks skin and connective tissue diseases Aged 80 and over prostate cancer stem cells Middle Aged prostate cancer Up-Regulation Gene Expression Regulation Neoplastic Neuroendocrine Tumors Prostatic Neoplasms Castration-Resistant Oncology Receptors Androgen 030220 oncology & carcinogenesis Disease Progression Neoplastic Stem Cells Immunohistochemistry Adenocarcinoma Taxoids Signal Transduction Research Paper medicine.medical_specialty medicine.drug_class MUC1 digestive system Disease-Free Survival 03 medical and health sciences DU145 Downregulation and upregulation Cell Line Tumor Biomarkers Tumor medicine Animals Humans metastasis RNA Messenger neoplasms Aged business.industry Mucin-1 Gene Amplification Computational Biology Prostatic Neoplasms medicine.disease Androgen Antineoplastic Agents Phytogenic Survival Analysis Xenograft Model Antitumor Assays biological factors digestive system diseases Androgen receptor 030104 developmental biology Cancer research business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.13073 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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