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Alterations in Tumor Aggression Following Androgen Receptor Signaling Restoration in Canine Prostate Cancer Cell Lines.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Aug 07; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
-
Abstract
- In prostate cancer (PCa), androgens upregulate tumorigenesis, whereas in benign tissue, the revival of androgen receptor (AR) signaling suppresses aggressive behaviors, suggesting therapeutic potential. Dogs, natural PCa models, often lack AR in PCa. We restored AR in dog PCa to investigate resultant characteristics. Three AR-null canine PCa lines (1508, Leo, 1258) were transfected with canine wild-type AR and treated with dihydrotestosterone (DHT). In 1508, AR restoration decreased clonogenicity ( p = 0.03), viability ( p = 0.004), migration ( p = 0.03), invasion ( p = 0.01), and increased expression of the tumor suppressor NKX3.1 , an AR transcriptional target ( p = 0.001). In Leo, AR decreased clonogenicity ( p = 0.04) and the expression of another AR transcriptional target FOLH1 ( p < 0.001) and increased the expression of NKX3.1 ( p = 0.01). In 1258, AR increased migration ( p = 0.006) and invasion ( p = 0.03). Epithelial-mesenchymal transition (EMT) marker ( Vimentin , N-cadherin , SNAIL1 ) expression increased with AR restoration in Leo and 1258 but not 1508; siRNA vimentin knockdown abrogated AR-induced 1258 migration only. Overall, 1508 showed AR-mediated tumor suppression; AR affected proliferation in Leo but not migration or invasion; and EMT and AR regulated migration and invasion in 1258 but not proliferation. This study highlights the heterogeneous nature of PCa in dogs and cell line-specific effects of AR abrogation on aggressive behaviors.
- Subjects :
- Animals
Dogs
Male
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Neoplasm Invasiveness
Cell Proliferation
Receptors, Androgen metabolism
Receptors, Androgen genetics
Signal Transduction
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Prostatic Neoplasms genetics
Epithelial-Mesenchymal Transition genetics
Cell Movement
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39201315
- Full Text :
- https://doi.org/10.3390/ijms25168628