Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells
Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, espec...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1404 |
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| author | Hye-Jin You Byong-Chul You Jong-Kwang Kim Jae-Min Park Bo-Seul Song Jae-Kyung Myung |
| author_facet | Hye-Jin You Byong-Chul You Jong-Kwang Kim Jae-Min Park Bo-Seul Song Jae-Kyung Myung |
| author_sort | Hye-Jin You |
| collection | DOAJ |
| description | Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC. |
| first_indexed | 2024-03-10T06:42:06Z |
| format | Article |
| id | doaj.art-12b94a36520c412397d6b073a0187f3b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:42:06Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-12b94a36520c412397d6b073a0187f3b2023-11-22T17:31:23ZengMDPI AGBiomedicines2227-90592021-10-01910140410.3390/biomedicines9101404Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer CellsHye-Jin You0Byong-Chul You1Jong-Kwang Kim2Jae-Min Park3Bo-Seul Song4Jae-Kyung Myung5Division of Translational Science, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaDivision of Translational Science, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaResearch Core Center, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaDepartment of Cancer Biomedical Science, National Cancer Center-Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaDepartment of Cancer Biomedical Science, National Cancer Center-Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaDepartment of Cancer Biomedical Science, National Cancer Center-Graduate School of Cancer Science and Policy, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, KoreaAndrogen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC.https://www.mdpi.com/2227-9059/9/10/1404castration resistant prostate cancerproteomemetabolitessignaling pathwayandrogen |
| spellingShingle | Hye-Jin You Byong-Chul You Jong-Kwang Kim Jae-Min Park Bo-Seul Song Jae-Kyung Myung Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells Biomedicines castration resistant prostate cancer proteome metabolites signaling pathway androgen |
| title | Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells |
| title_full | Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells |
| title_fullStr | Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells |
| title_full_unstemmed | Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells |
| title_short | Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells |
| title_sort | characterization of proteins regulated by androgen and protein kinase a signaling in vcap prostate cancer cells |
| topic | castration resistant prostate cancer proteome metabolites signaling pathway androgen |
| url | https://www.mdpi.com/2227-9059/9/10/1404 |
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