Induction and function of CYR61 (CCN1) in prostatic stromal and epithelial cells: CYR61 is required for prostatic cell proliferation
Abstract
BACKGROUND: CYR61 is an extracellular matrix‐associated protein that promotes adhesion, migration, and proliferation of endothelial cells and fibroblasts. Prostate enlargement, which frequently causes the urethral compression, is often histologically observed as stromal and epithelial hyperplasia in an enlarged gland. To determine whether or not CYR61 has relevance to the progression of benign prostatic hyperplasia (BPH), we investigated the induction of CYR61, and also examined its function in both prostatic stromal and epithelial cells. METHODS: Recombinant CYR61 protein was used for the examination of the activity of CYR61 as to cell adhesion and proliferation. Quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was utilized to screen for inducers of the CYR61 gene in prostatic cells. Finally, the effects of an anti‐sense oligonucleotide, which could reduce the production of CYR61, on the morphology and growth of prostatic cells were also examined. RESULTS: Recombinant CYR61 protein promotes prostatic cell adhesion and proliferation. The mRNA for CYR61, a growth factor‐inducible immediate early gene, was markedly induced by fetal bovine serum (FBS) within 1 hr, and strongly induced by transforming growth factor‐β1 (TGF‐β) for at least 19 hr following stimulation. The suppression of CYR61 production with an anti‐sense oligonucleotide causes obvious morphological changes of prostatic cells. Furthermore, we have shown that CYR61 is necessary, at least in part, for FBS‐induced prostatic cell proliferation, because dramatic inhibition of cellular growth was caused by the suppression of CYR61 production with the addition of the anti‐sense oligonucleotide before FBS stimulation. CONCLUSIONS: In this study, we demonstrate that serum growth factors induce the CYR61 gene in both stromal and epithelial cells, and that CYR61 plays functional roles in cell adhesion, morphology, and proliferation, supporting its involvement in benign prostatic enlargement. These results strongly suggest that CYR61 is a key molecule, and therefore could be a potential therapeutic target in prostatic hyperplastic growth. © 2004 Wiley‐Liss, Inc.
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This activity may contribute to CCN1's ability to promote growth factor-induced proliferation in PC3 prostate cancer cells and ovarian carcinoma cells, and IL-17-stimulated proliferation in synoviocytes.
“This activity may contribute to its ability to promote growth factor-induced poliferation in PC3 prostate cancer cells [76,77] and ovarian carcinoma cells [78], and IL-17-stimulated proliferation in synoviocytes [79].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [76]
CCN1 can exacerbate apoptosis of prostate cancer cells in the presence of TRAIL.
“For example, whereas CCN1 can promote the proliferation of prostate cancer cells, CCN1 can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL [74,76,77].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [76]
CCN1 can promote proliferation of prostate cancer cells.
“For example, whereas CCN1 can promote the proliferation of prostate cancer cells, CCN1 can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL [74,76,77].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [76]
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CCN1/CYR61: the very model of a modern matricellular protein
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- Authors
- Sakamoto, S., Yokoyama, M., Aoki, M., Suzuki, K., Kakehi, Y., & Saito, Y.
- Affiliations
- Japan Tobacco (Japan) (JP)
- Kagawa University (JP)
- Corresponding author
- Sakamoto, Shinji
- Venue
- The Prostate
- Publisher
- Wiley
- Published
- 2004-04-22
- Volume
- 61
- Issue
- 4
- Pages
- 305-317
- ISSN
- 0270-4137 (ISSN-L)
- 1097-0045
- OpenAlex
- W2065507165
- Cited by
- 33
- References
- 43
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2012: 5
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Prostate (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- CYR61, benign prostatic hyperplasia, prostate stromal cells, prostate epithelial cells, cell proliferation, cell adhesion, extracellular matrix, TGF-β1, fetal bovine serum, antisense oligonucleotides, gene induction, therapeutic target
- MeSH terms
- Cell Adhesion, Cell Line, Epithelial Cells, Fetal Blood, Gene Expression Regulation, Growth Substances, Humans, Male, Prostate, Prostatic Hyperplasia, Recombinant Proteins, Oligonucleotides, Antisense, Stromal Cells, Immediate-Early Proteins, Reverse Transcriptase Polymerase Chain Reaction, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Cysteine-Rich Protein 61
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