Chhabra Alok, Fernando Herman, Watkins Gareth, Mansel Robert E, Jiang Wen G
Metastasis and Angiogenesis Research Group, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
Oncol Rep. 2007 Oct;18(4):953-8.
It has been suggested that the cAMP responsive element-binding protein (CREB) may act as a transcription regulator of aromatase in breast cancer cells. However, there is little knowledge on the expression of CREB1 in human breast cancer and its clinical significance. The current study investigated the expression pattern of CREB1 in human breast cancer at the mRNA and protein level and correlated it with the clinical outcome. CREB1 staining was primarily seen in the nucleus of both normal and tumour cells. At the mRNA level, we found a significantly higher level of CREB1 in breast tumour tissues (n=120) as compared to non-neoplastic mammary tissues (n=33, p=0.0092). When compared between different histological types CREB1 expression was significantly higher in ductal carcinoma as compared to lobular and other breast carcinoma. Patients with a poor prognosis and with metastasis had a markedly raised level of CREB1 compared to patients who were disease free. In addition, node-positive tumours had higher levels of CREB1 than node-negative tumours (p=0.0018). Finally, patients with high levels of CREB1 had a significantly shorter disease-free survival [95.3 (68.4-122.3, 95% CI) months] compared with those with lower levels [133.9 (123.5-144.2) months, p=0.0193]. This study demonstrates that the level of CREB1 in breast cancer patients is elevated and is significantly raised in patients with a poor prognosis, metastatic disease and nodal involvement. We conclude that the level of CREB1 expression is aberrant in human breast cancer and is associated with disease progression in breast cancer patients.
有人提出，环磷酸腺苷反应元件结合蛋白（CREB）可能作为乳腺癌细胞中芳香化酶的转录调节因子。然而，关于CREB1在人类乳腺癌中的表达及其临床意义知之甚少。当前的研究在mRNA和蛋白质水平上调查了CREB1在人类乳腺癌中的表达模式，并将其与临床结果相关联。CREB1染色主要见于正常细胞和肿瘤细胞的细胞核。在mRNA水平上，我们发现与非肿瘤性乳腺组织（n = 33，p = 0.0092）相比，乳腺肿瘤组织（n = 120）中CREB1的水平显著更高。在不同组织学类型之间进行比较时，与小叶癌和其他乳腺癌相比，导管癌中CREB1的表达显著更高。与无疾病的患者相比，预后不良和有转移的患者CREB1水平明显升高。此外，淋巴结阳性肿瘤的CREB1水平高于淋巴结阴性肿瘤（p = 0.0018）。最后，与CREB1水平较低的患者[133.9（123.5 - 144.2）个月]相比，CREB1水平较高的患者无病生存期明显更短[95.3（68.4 - 122.3，95%可信区间）个月，p = 0.0193]。这项研究表明，乳腺癌患者中CREB1水平升高，在预后不良、有转移性疾病和有淋巴结受累的患者中显著升高。我们得出结论，CREB1在人类乳腺癌中的表达水平异常，并且与乳腺癌患者的疾病进展相关。
