Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
| Autor: | Sandra Karlsson, Maria Araceli Diaz Cruz, Maria Faresjö, Ferenc Szekeres, Dennis Larsson, Dan Lund |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Protein Disulfide-Isomerases PDIA3 Biology medicine.disease_cause urologic and male genital diseases Calcitriol receptor Gene Expression Regulation Enzymologic Prostate cancer DU145 Cell Line Tumor LNCaP Genetics medicine Humans Amino Acid Sequence RNA Messenger Vitamin D Receptor Molecular Biology Neoplasm Staging VDR Cancer och onkologi Base Sequence Prostatic Neoplasms Cancer General Medicine Androgen dependency PDIA3N medicine.disease Gene Expression Regulation Neoplastic Isoenzymes Cancer and Oncology Cancer research Original Article Carcinogenesis |
| Zdroj: | Molecular Biology Reports |
| Popis: | Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-021-06277-1. |
| Databáze: | OpenAIRE |
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