Downregulation of the potential suppressor gene IGFBP-rP1 in human breast cancer is associated with inactivation of the retinoblastoma protein, cyclin E overexpression and increased proliferation in estrogen receptor negative tumors
Downregulation of the potential suppressor gene IGFBP-rP1 in human breast cancer is associated with inactivation of the retinoblastoma protein, cyclin E overexpression and increased proliferation in estrogen receptor negative tumors
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DOI：
10.1038/sj.onc.1204471
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发表时间：
2001-06-14
期刊：
影响因子：
8
通讯作者：
Seth, A
中科院分区：
文献类型：
--
作者：
Landberg, G;Östlund, H;Seth, A
由配体、受体和结合蛋白组成的复杂的胰岛素样生长因子网络已被证明在乳腺癌中受到干扰，除了控制细胞周期检查点的蛋白质缺陷外，这种类型的畸变还可能影响肿瘤的生长和存活，从而影响肿瘤的侵袭性和对治疗的潜在反应。我们之前已经鉴定出 T1A12/mac25 蛋白，它与 IGFBP-rP1 相同， 作为乳腺癌细胞与正常细胞相比的差异表达基因产物，在这里，我们比较了 106 个肿瘤样本中 IGFBP-rP1 的表达与已知的细胞周期畸变状态和其他临床病理学数据，这是使用肿瘤组织切片阵列系统完成的，该系统允许同时对所有样本进行平行免疫组织化学染色，在大多数肿瘤中观察到不同强度的细胞质染色， 15%完全缺乏IGFBP-rP1染色，20%弱染色，32%中等和33%强染色，低IGFBP-rP1与高细胞周期蛋白E蛋白含量、视网膜母细胞瘤蛋白(pRb)失活、低bcl-2蛋白、低分化肿瘤和较高分期相关，低IGFBP-rP1蛋白患者的预后显着受损 有趣的是，IGFBP-rP1 在雌激素受体阴性肿瘤以及细胞周期蛋白 E 高肿瘤中显示出与增殖呈负相关（Ki-67%），这表明 IGFBP-rP1 具有独立的细胞周期调节功能，独立于与雌激素受体或 pRb 途径的相互作用。
The complex insulin-like growth factor network of ligands, receptors and binding proteins has been shown to be disturbed in breast cancer, In addition to defects in proteins controling cell cycle checkpoints, this type of aberrations could affect tumor growth and survival thereby influencing both tumor aggressiveness and potential response to treatments, We have previously identified the T1A12/mac25 protein, which is identical to the IGFBP-rP1, as a differentially expressed gene product in breast cancer cells compared with normal cells, Here we compare the expression of IGFBP-rP1 in 106 tumor samples with known status of cell cycle aberrations and other clinicopathological data, This was done using a tumor tissue section array system that allows for simultaneous immunohistochemical staining of ail samples in parallel, Cytoplasmic staining of variable intensity was observed in most tumors, 15% Lacked IGFBP-rP1 staining completely, 20% had weak staining, 32% intermediate and 33% showed strong staining, Low IGFBP-rP1 was associated with high cyclin E protein content, retinoblastoma protein (pRb) inactivation, low bcl-2 protein, poorly differentiated tumors and higher stage, There was a significantly impaired prognosis for patients with low IGFBP-rP1 protein tumors, Interestingly, IGFBP-rP1 showed an inverse association with proliferation (Ki-67%) in estrogen receptor negative tumors as well as in cyclin E high tumors suggesting a separate cell cycle regulatory function for IGFBP-rP1 independent of interaction with the estrogen receptor or the pRb pathway.