Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Jiang, Wen Guo; Watkins, Gareth; Fodstad, Øystein; Douglas-Jones, Anthony; Mokbel, Kefah; Mansel, Robert Edward

doi:10.1677/erc.1.00825

Cited by 159 publications

(145 citation statements)

References 29 publications

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“…CCN1 protein is found at higher levels in breast cancer samples compared with adjacent nontumor tissue, and staining of CCN1 in tumors positively correlates with American Joint Committee on Cancer (AJCC) disease stages I-IV. Of additional significance, a strong association was also found between lymph node involvement and high CCN1 expression in patients with invasive breast cancer (Jiang et al, 2004). Both in vitro and in vivo studies document that overexpression of CCN1 in breast cancer cells upregulates MAPK signaling in an integrin avb3-dependent manner Vellon et al, 2005;O'Kelly et al, 2008).…”

Section: Introductionmentioning

confidence: 87%

“…Alternatively, CCN1 has a complex role in tumorigenesis, showing divergent functions and expression profiles in cancers from different tissues (O'Kelly, 2005). Increased expression of CCN1 occurs in several cancer indications, that is, human breast cancers, malignant gliomas, gastric adenocarcinomas and melanomas (Jiang et al, 2004;O'Kelly et al, 2008). CCN1 protein is found at higher levels in breast cancer samples compared with adjacent nontumor tissue, and staining of CCN1 in tumors positively correlates with American Joint Committee on Cancer (AJCC) disease stages I-IV.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

Dash

Lee

et al. 2010

Oncogene

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Enhanced expression of the CCN family of secretory integrin-binding proteins correlates with many essential components of the cancerous state, including tumor cell adhesion, proliferation, invasion and migration. Consequently, CCN1 expression is elevated in various cancers, including breast cancer, and its expression directly correlates with poor patient prognosis. Using subtraction-hybridization, combined with induction of cancer cell terminal differentiation, we cloned SARI (suppressor of activator protein (AP)-1, regulated by interferon (IFN)), an IFN-b-inducible, potent tumor suppressor gene that exerts cancer-selective growth inhibitory effects. Forced expression of SARI using an adenovirus (Ad.SARI) inhibits AP-1 function and downregulates CCN1 expression in multiple cancer lineages, resulting in a profound inhibition in anchorage-independent cell growth and tumor cell invasion. Overexpression of SARI reduces CCN1-promoter activity through inhibition of AP-1 binding. Accordingly, SARI selectively blocks expression of the transformed state in rat embryo fibroblast cells that stably overexpress c-Jun. These results illustrate that SARI inhibits AP-1 transactivating factor binding to the ciselement of the CCN1 promoter, possibly through its interaction with c-Jun. Overall, SARI can directly inhibit CCN1-induced transformation by inhibiting the transcription of CCN1, as well as indirectly by inhibiting the expression of c-Jun (and hence blocking AP-1 activity). In these contexts, transformed cells 'addicted' to AP-1 activity are rendered susceptible to SARI-mediated inhibition of expression of the transformed phenotype.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

Dash

Lee

et al. 2010

Oncogene

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“…Levels of the Com-1 transcript are shown in 2 ways: Com-1 transcript and Com-1/CK19 ratio, as we have reported recently. 15 Quantitation of the ER and ER-b were described previously. 13 Primers given in Table I.…”

Section: Quantitative Analysis Of Com-1 Transcriptmentioning

confidence: 99%

“…15 Frozen sections of breast tumours and background tissues 6 lm thick were cut using a cryostat. The sections were mounted on Super-Frost Plus microscope slides, air dried and then fixed in a mixture of 50% acetone and 50% methanol.…”

Section: Immunohistochemical Staining Of Com-1 and Oestrogen Receptorsmentioning

confidence: 99%

Expression of Com‐1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Jiang

Watkins

Douglas-Jones

et al. 2005

Intl Journal of Cancer

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Com‐1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com‐1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n‐120) with matched normal non‐neoplastic mammary tissues (n = 32) were used. Expression of Com‐1 in cancer cells and mammary tissues were studied using conventional and real‐time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann‐Whitney U‐test and Cox Proportion analysis. Com‐1 was expressed in breast cancer cell lines. Com‐1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com‐1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com‐1, compared to normal non‐neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 ± 135 copies of Com1 transcript, 44.3 ± 36 and 0.64 ± 0.24, respectively, p = 0.06 by Kruskal‐Wallis test). Likewise, node positive tumours had low levels of Com‐1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 ± 7 copies of Com1 transcript), had local recurrence (41.5 ± 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 ± 0.03 copies of Com1 transcript) had lower levels of Com‐1, when compared to tumours from patients who remained disease free (156 ± 129 copies of Com1 transcript). There was no significant correlation between Com‐1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com‐1 in ER‐β positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow‐up 120 months). Com‐1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com‐1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com‐1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status. © 2005 Wiley‐Liss, Inc.

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“…Immunohistochemical staining was performed using a standard technique employed in our laboratories (3,4). The tissues were frozen-sectioned using a Leica cryostat, at an 8-µm thickness.…”

Section: Methodsmentioning

confidence: 99%

Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute and chronic wounds

Minhas

Martin

Ruge

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. The CCN family is a group of extremely cysteinerich proteins that are found within the extracellular matrix and are comprised of cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN 2) and nephroblastoma overexpressed (NOV/CCN3). Collectively, these proteins stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration, and regulate angiogenesis, tumour growth, placentation, implantation, embryogenesis and endochondral ossification. Despite such diverse activity, CCN protein function has not been explored in human wounds and healing. In the present study, we investigated the expression of these proteins in samples of normal, acute and chronic wounds using immunohistochemical staining and real-time quantitative RT-PCR. Statistical analysis was performed using the Fisher's exact test. Our results showed that, although all CCN proteins were present in normal, acute and chronic wounds, their expression levels differed, particularly in the case of connective tissue growth factor (CTGF), for which significantly reduced levels were found in chronic wounds compared to acute wounds (p<0.002). Thus, the lack of CTGF in wound tissues may contribute to the abnormal healing of clinical wounds. This suggests that CCN proteins may play an important role in human tissue wound healing. This further suggests that human wound healing may be promoted by manipulating the levels of this protein.

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Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer

Cited by 159 publications

References 29 publications

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

Expression of Com‐1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute and chronic wounds

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