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Cited by 146Connective Tissue Growth Factor ResearchAngiogenesis and VEGF in CancerCancer Mechanisms and Therapy

Breast Cancer

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Xie, Dong, Miller, Carl W., O'Kelly, James, Nakachi, Kei, Sakashita, Akiko, Said, Jonathan W., Gornbein, Jeffrey, Koeffler, H. Phillip·2001·Journal of Biological Chemistry
DOI 10.1074/jbc.m009755200
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Abstract

To identify genes involved in breast cancer, polymerase chain reaction-selected cDNA subtraction was utilized to construct a breast cancer-subtracted library. Differential screening of the library isolated the growth factor-inducible immediate-early gene Cyr61, a secreted, cysteine-rich, heparin binding protein that promotes endothelial cell adhesion, migration, and neovascularization. Northern analysis revealed that Cyr61 was expressed highly in the invasive breast cancer cell lines MDA-MB-231, T47D, and MDA-MB-157; very low levels were found in the less tumorigenic MCF-7 and BT-20 breast cancer cells and barely detectable amounts were expressed in the normal breast cells, MCF-12A. Univariate analysis showed a significant or borderline significant association between Cyr61 expression and stage, tumor size, lymph node positivity, age, and estrogen receptor levels. Interestingly, expression of Cyr61 mRNA increased 8- to 12-fold in MCF-12A and 3- to 5-fold in MCF-7 cells after 24- and 48-h exposure to estrogen, respectively. Induction of Cyr61 mRNA was blocked by tamoxifen and ICI182,780, inhibitors of the estrogen receptor. Stable expression of Cyr61 cDNA under the regulation of a constitutive promoter in MCF-7 cells enhanced anchorage-independent cell growth in soft agar and significantly increased tumorigenicity and vascularization of these tumors in nude mice. Moreover, overexpression of Cyr61 in MCF-12A normal breast cells induced their tumor formation and vascularization in nude mice. In summary, these results suggest that Cyr61 may play a role in the progression of breast cancer and may be involved in estrogen-mediated tumor development.

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  • CCN1 expression significantly correlates with stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer, prostate cancer, glioma, gastric adenocarcinoma, and squamous cell carcinoma.

    “The clinical relevance of these observations is supported by the finding of a significant correlation between CCN1 expression and the stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer [142,145–148], prostate cancer [149], glioma [150], gastric adenocarcinoma [151], and squamous cell carcinoma [143].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [142]

  • 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 [142]

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Authors
Xie, D., Miller, C. W., O'Kelly, J., Nakachi, K., Sakashita, A., Said, J. W., Gornbein, J., & Koeffler, H. P.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Saitama Cancer Center (JP)
  • University of California, Los Angeles (US)
Corresponding author
Xie, Dong
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-04
Volume
276
Issue
17
Pages
14187-14194
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m009755200
OpenAlex
W1497165801
Cited by
146
References
39
Citations by year
2025: 2 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 4 · 2013: 11 · 2012: 7
FWCI
4.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
Keywords
breast cancer, CYR61, estrogen receptor, tamoxifen, fulvestrant, tumor vascularization, anchorage-independent growth, tumor progression, MCF-7 cells, MCF-12A cells, heparin-binding protein, gene expression profiling
MeSH terms
Fulvestrant, Adult, Age Factors, Aged, Aged, 80 and over, Animals, Breast Neoplasms, Cell Movement, Cells, Cultured, Estradiol, Estrogen Antagonists, Estrogens, Female, Growth Substances, Humans, Mice, Nude, Middle Aged, Neoplasm Transplantation, Promoter Regions, Genetic, Protein Binding, Receptors, Estrogen, Recombinant Proteins, Tamoxifen, Time Factors, Transfection, Tumor Cells, Cultured, Blotting, Northern, Gene Library, Multivariate Analysis, Immediate-Early Proteins, DNA, Complementary, Carcinoma, Ductal, Breast, Disease Progression, Antineoplastic Agents, Hormonal, Reverse Transcriptase Polymerase Chain Reaction, Intercellular Signaling Peptides and Proteins, Mice, Cysteine-Rich Protein 61

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