Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer.
Dystroglycan is frequently lost in adenocarcinoma, but the mechanisms and consequences are poorly understood. We report an analysis of β-dystroglycan in prostate cancer in human tissue samples and in LNCaP cells in vitro. There is progressive loss of β-dystroglycan immunoreactivity from basal and lateral surfaces of prostate epithelia which correlates significantly with increasing Gleason grade. In about half of matched bone metastases there is significant dystroglycan re-expression. In tumour tissue and in LNCaP cells there is also a tyrosine phosphorylation-dependent translocation of β-dystroglycan to the nucleus. Analysis of gene expression data by microarray, reveals that nuclear targeting of β-dystroglycan in LNCaP cells alters the transcription of relatively few genes, the most unregulated being the transcription factor ETV1. These data suggest that proteolysis, tyrosine phosphorylation and translocation of dystroglycan to the nucleus resulting in altered gene transcription could be important mechanisms in the progression of prostate cancer.
1] Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK [2].
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G
Mathew
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A
Mitchell
J M
JM
Down
L A
LA
Jacobs
F C
FC
Hamdy
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C
Eaton
D J
DJ
Rosario
S S
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Cross
S J
SJ
Winder
D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D019814:Myristic Acid / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000728:Androgens; D014157:Transcription Factors; D019814:Myristic Acid; D049030:Dystroglycans; D019000:Phosphotyrosine