Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer
Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer
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DOI：
10.1677/erc.1.00825
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发表时间：
2004-12-01
影响因子：
3.9
通讯作者：
Mansel, RE
中科院分区：
文献类型：
--
作者：
Jiang, WG;Watkins, G;Mansel, RE
CCN家族成员富含半胱氨酸61（Cyr 61/CCN 1）、结缔组织生长因子（CTGF/CCN 2）和肾母细胞瘤过表达（Nov/CCN 3）在细胞中发挥不同的作用，已知其调节细胞生长、粘附、基质产生和迁移，并且参与各种细胞类型中的内分泌调节途径。这些分子在癌症中的作用仍然存在争议。在一组122人乳腺肿瘤（连同32个正常乳腺组织），我们分析了所有三个CCN成员在mRNA和蛋白质水平的表达。与正常组织相比，肿瘤组织中Cyr 61的水平显著较高（P = 0.02），但CTGF和Nov的水平较低。Cyr 61水平显著升高与预后差（P = 0.02）、淋巴结受累（P = 0.03）和转移性疾病（P = 0.016）相关。死于乳腺癌的患者也有高水平的Cyr 61。而预后差（P = 0.021）、有转移（P = 0.012）、局部复发（P = 0.0024）和死亡（P = 0.0072）的患者CTGF水平明显降低。与CTGF相似，低水平的Nov也见于预后差、死亡率低和生存率显著降低的患者（分别为P = 0.033和P = 0.0146）。冷冻切片组织的免疫组织化学分析完全支持这一结果。虽然成纤维细胞和内皮细胞通常表达良好水平的所有三种CCN蛋白，但高度侵袭性的MDA MB 231细胞表达较低水平的CTGF和Nov，但比侵袭性较低的MCF-7表达较高水平的Cyr 61。它的结论是，CCN家族的成员差异表达，并可能发挥重要的，但对比的作用，在人类乳腺癌的进行性。虽然Cyr 61似乎是刺激攻击性的因素，但CTGF和Nov可能是肿瘤抑制剂。
The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrine-regulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 (P = 0.02), but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis (P = 0.02), nodal involvement (P = 0.03) and metastatic disease (P = 0.016). Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis (P = 0.021), metastasis (P = 0.012), local recurrence (P = 0.0024) and mortality (P = 0.0072) had markedly reduced levels. Similar to CTGF, low levels of Nov were also seen in patients with poor prognosis and mortality and with significantly decreased survival (P = 0.033 and P = 0.0146, respectively). This result was fully supported by immunohistochemical analysis of frozen sectioned tissues. While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7. It is concluded that members of the CCN family are differentially expressed and may play important but contrasting roles in the progressive nature of human breast cancer. While Cyr61 appears to act as a factor stimulating aggressiveness, CTGF and Nov may act as tumour suppressors.