Ovarian Carcinomas: CCN Genes Are Aberrantly Expressed and CCN1 Promotes Proliferation of these Cells
Abstract
Purpose: The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family consists of six matricellular proteins that are involved in various cellular functions, such as proliferation, development, and angiogenesis. The purpose of this study was to explore the possibility that CCN genes are involved in ovarian cancers. Experimental Design: We quantified CCN expression in a series of 59 ovarian cancers using quantitative real-time reverse transcription-PCR. CCN1 protein levels were further determined by immunohistochemistry and Western blot analysis. Overexpression and inhibition of CCN1 expression by small interfering RNA were used to examine its role in ovarian cancer cell proliferation in vitro and in vivo. Results: We found dysregulation of levels of the various CCN mRNAs in ovarian cancers compared with their expression in normal whole ovaries. Expression of CCN1 protein was detected in normal ovarian epithelial cells and ovarian tumors as well as in ovarian cancer cell lines. Furthermore, estrogen increased CCN1 mRNA and protein levels in ovarian cancer cells. Ectopic expression of CCN1 enhanced the growth of ovarian cancer cells in liquid culture, whereas inhibition of its expression decreased proliferation and increased apoptosis in these cells. The observed changes in cell growth were accompanied with activation of Akt and extracellular signal-regulated kinase (ERK) signaling pathways. Stable expression of CCN1 in SKOV3 cells significantly increased tumorigenicity in nude mice. Finally, overexpression of CCN1 conferred resistant to carboplatin-induced apoptosis in SKOV3 cells. Conclusions: This is the first study to show abnormalities in CCN expression in ovarian carcinomas. Furthermore, our results suggest that CCN1 may play a role in ovarian carcinogenesis by stimulating survival and antiapoptotic signaling pathways.
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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 [78]
Forced expression of CCN1 enhanced tumor growth in xenografts of breast cancer cells, prostate cancer cells, ovarian carcinoma cells, and squamous carcinoma cells.
“Accordingly, subsequent studies have shown that forced expression of CCN1 enhanced tumor growth in xenografts of breast cancer cells [142], prostate cancer cells [74], ovarian carcinoma cells [78], and squamous carcinoma cells [143].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [78]
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- Authors
- Gery, S., Xie, D., Yin, D., Gabra, H., Miller, C., Wang, H., Scott, D., Yi, W. S., Popoviciu, M. L., Said, J. W., & Koeffler, H. P.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Imperial College London (GB)
- 2Biomathematics and
- Edinburgh Cancer Research (GB)
- University of California, Los Angeles (US)
- Venue
- Clinical Cancer Research
- Published
- 2005-10-15
- Volume
- 11
- Issue
- 20
- Pages
- 7243-7254
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2113317460
- Cited by
- 97
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- ovarian carcinoma, CCN family, CYR61, connective tissue growth factor, matricellular proteins, gene overexpression, cell proliferation, apoptosis, Akt signaling, ERK signaling, estrogen, carboplatin resistance, tumorigenicity, SKOV3 cells, ovarian carcinogenesis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Cisplatin, Epithelial Cells, Female, Humans, Immunohistochemistry, Mice, Nude, Middle Aged, Neoplasm Transplantation, Neoplasms, Experimental, Ovarian Neoplasms, Transfection, Transplantation, Heterologous, Blotting, Northern, Blotting, Western, Gene Expression Regulation, Neoplastic, Carboplatin, Apoptosis, Immediate-Early Proteins, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Cell Proliferation, Mice, Cysteine-Rich Protein 61
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