Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma
Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma
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DOI：
10.1016/s0046-8177(99)90117-x
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发表时间：
1999-04-01
期刊：
影响因子：
3.3
通讯作者：
Ittmann, M
中科院分区：
文献类型：
--
作者：
Giri, D;Ittmann, M
PTEN肿瘤抑制基因编码的双特异性蛋白磷酸酶可能在调节整合素介导的信号中发挥关键作用。在一小部分临床局限性前列腺癌中检测到PTEN基因失活，但在转移性疾病中很常见。在胶质母细胞瘤细胞系中已经显示，染色体10 q（PTEN gem位于该染色体10 q处）的丢失与条件培养基中血管生成活性的增加相关，这可归因于血小板反应蛋白-1（血管生成的负调节因子）的下调。因此，我们希望确定PTEN的失活是否可能与前列腺癌中血管生成的增加有关，因为局部癌症中血管生成的增加与转移性疾病的发展有关。血管生成进行了评估后，在8例证实纯合性缺失的PTEN基因和24例对照组的抗第VIII因子相关抗原抗体免疫染色的最大新生血管的区域计数微血管。PTEN失活与微血管计数增加之间存在统计学显著相关性。在所有Gleason评分中，与具有相同评分的对照病例相比，具有PTEN失活的病例中的微血管密度更高。为了确定是否与PTEN失活的情况下，血管生成的增加是由血管生成抑制剂血小板反应蛋白-1的表达下调引起的，我们分析了一个子集的情况下，通过免疫染色与抗血小板反应蛋白-1抗体。大约25%的病例显示前列腺癌细胞染色减少，但与PTEN失活无关。因此，PTEN失活与血管生成增加有关，但血管生成增加并不归因于血小板反应蛋白-1表达的下调。版权所有（C）1999 W.B.桑德斯公司
The PTEN tumor suppressor gene encodes a dual-specificity protein phosphatase that may play a key role in modulating integrin-mediated signals. Inactivation of the PTEN gene has been detected in a small percentage of clinically localized prostate cancers but is common in metastatic disease. It has been shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gem is located, is associated with increased angiogenic activity in the conditioned medium attributable to downregulation of thrombospondin-l, a negative regulator of angiogenesis. Therefore, we wished to determine whether inactivation of PTEN might be associated with increased angiogenesis in prostate cancers, because increased angiogenesis in localized cancers is associated with development of metastatic disease. Angiogenesis was assessed by counting microvessels in areas of maximal neovascularization after immunostaining with anti-factor VIII-related antigen antibodies in eight cases with proven homozygous deletion of the PTEN gene and 24 control cases. There was: a statistically significant correlation between PTEN inactivation and increased microvessel counts. The microvessel density was higher at all Gleason scores in the cases with PTEN inactivation compared with control cases with the same score. To determine whether the increased angiogenesis in cases with PTEN inactivation was caused by downregulation of expression of the angiogenesis inhibitor thrombospondin-l, we analyzed a subset of the cases by immunostaining with anti-thrombospondin-1 antibody. Approximately 25% of cases showed decreased staining of prostate cancer cells, but there was no correlation with PTEN inactivation. Thus, PTEN inactivation is associated with increased angiogenesis, but the increased, angiogenesis is not attributable to downregulation of thrombospondin-1 expression. Copyright (C) 1999 by W.B. Saunders Company.