Santagata Sandro, Demichelis Francesca, Riva Alberto, Varambally Sooryanarayana, Hofer Matthias D, Kutok Jeffery L, Kim Robert, Tang Jeffery, Montie James E, Chinnaiyan Arul M, Rubin Mark A, Aster Jon C
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 2004 Oct 1;64(19):6854-7. doi: 10.1158/0008-5472.CAN-04-2500.
Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters. These findings support a model in which dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers.
最近的研究表明，NOTCH信号传导可促进上皮-间质转化，并通过AKT增强信号传导，AKT是上皮细胞尤其是前列腺癌中重要的生长和存活途径。在此，我们通过对154名男性的人类肿瘤样本中JAGGED1表达进行免疫组织化学分析发现，与局限性前列腺癌或良性前列腺组织相比，NOTCH受体配体JAGGED1在转移性前列腺癌中表达明显更高。此外，在一部分临床局限性肿瘤中，JAGGED1的高表达与复发显著相关，且独立于其他临床参数。这些发现支持了一种模型，即JAGGED1蛋白水平的失调在前列腺癌进展和转移中起作用，并表明JAGGED1可能是区分惰性和侵袭性前列腺癌的有用标志物。
