Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells.
Prostate cancer, the most frequently diagnosed cancer in Western men, can display a high variability in term of clinical aggressiveness and prognosis and none of the available markers is able to accurately predict its clinical course. Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton, respectively. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. This study investigated the role of DG in human prostate tumorigenesis and its suitability as a prognostic marker. The expression level of extracellular alpha-DG subunit was frequently reduced in human prostate cancer cell lines and primary tumors and the percentage of positive tumor cells was significantly further decreased in vivo following androgen ablation therapy (median = 1%) compared to pre-treatment samples (median = 28%). A significant relationship was observed between alpha-DG staining on the post-treatment samples and tumor recurrence. A dose- and time-dependent decrease of DG expression also occurred in human prostate cancer cells following treatment with the anti-androgen flutamide. Stable expression of an exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a marked inhibition of both anchorage-dependent and independent growth and of the in vivo tumorigenicity. These findings confirm and extend previous evidence that disturbances in the function of the DG complex might contribute to the definition of the malignant behavior of prostate cancer cells and suggest that androgens might regulate DG expression in these cells.
Sgambato
A
A
Laboratorio di Oncologia Molecolare, Centro di Riferimento Oncologico di Basilicata, Rionero in Vulture (PZ), Italy. asgambato@rm.unicatt.it
De Paola
B
B
Migaldi
M
M
Di Salvatore
M
M
Rettino
A
A
Rossi
G
G
Faraglia
B
B
Boninsegna
A
A
Maiorana
A
A
Cittadini
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D017097:Electric Impedance; D005485:Flutamide / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*
D000726:Androgen Antagonists; D000728:Androgens; D014408:Biomarkers, Tumor; D021122:Protein Subunits; D049030:Dystroglycans; D005485:Flutamide