Lederman Michal, Meir Tal, Zeschnigk Michael, Pe'er Jacob, Chowers Itay
Ophthalmology, Hadassah-Hebrew University Medical Center, Hebrew University School of Medicine, Jerusalem, Israel.
Curr Eye Res. 2008 Oct;33(10):876-84. doi: 10.1080/02713680802382989.
Members of the inhibitors of apoptosis proteins (IAPs) family are thought to promote tumor growth and interfere with response to therapy by suppressing apoptosis in several malignancies. We aimed to evaluate the expression of IAPs in uveal melanoma (UM) and its correlation with prognostic factors associated with death from metastatic UM.
Expression of eight IAP genes [Baculoviral IAP repeat-containing (BIRC) 1-8] was evaluated through reverse transcription (RT)-PCR. BIRC5 and BIRC7 expression was measured using quantitative PCR (QPCR). BIRC5 protein expression was assessed with immunohistochemistry. QPCR results were correlated with apoptosis rate and with prognostic factors in UM, including lesion dimensions, cell type, monosomy 3, and vascular mimicry patterns.
IAP genes were expressed in the majority of primary and metastatic UM. BIRC5 and BIRC7 levels were 8.8-fold (p = 0.0003) and 7.0-fold (p = 0.003) higher in tumors (primary and metastatic tissue) vs. normal eye tissue, respectively. BIRC5 levels correlated with presence of monosomy 3 (p = 0.01) and higher levels of BIRC7 correlated with epithelioid cell type (p = 0.048).
IAPs expression is up regulated in UM and is associated with some of its prognostic factors. Considering our findings together with previous reports on their role in a variety of malignancies and in UM cell lines, it is conceivable that IAPs contribute to the remarkable resistance of uveal melanoma to apoptosis-inducing chemotherapy.
凋亡抑制蛋白（IAPs）家族成员被认为可通过抑制多种恶性肿瘤中的细胞凋亡来促进肿瘤生长并干扰治疗反应。我们旨在评估IAPs在葡萄膜黑色素瘤（UM）中的表达及其与转移性UM死亡相关预后因素的相关性。
通过逆转录（RT）-PCR评估8个IAP基因[含杆状病毒IAP重复序列（BIRC）1-8]的表达。使用定量PCR（QPCR）测量BIRC5和BIRC7的表达。用免疫组织化学评估BIRC5蛋白表达。QPCR结果与UM中的凋亡率以及预后因素相关，包括病变大小、细胞类型、3号染色体单体性和血管拟态模式。
IAP基因在大多数原发性和转移性UM中表达。肿瘤（原发性和转移性组织）中BIRC5和BIRC7水平分别比正常眼组织高8.8倍（p = 0.0003）和7.0倍（p = 0.003）。BIRC5水平与3号染色体单体性的存在相关（p = 0.01），BIRC7水平较高与上皮样细胞类型相关（p = 0.048）。
IAPs在UM中表达上调，并与其一些预后因素相关。结合我们的研究结果以及先前关于它们在多种恶性肿瘤和UM细胞系中的作用的报道，可以想象IAPs促成了葡萄膜黑色素瘤对诱导凋亡化疗的显著抗性。
