Wu W, Fan Y H, Kemp B L, Walsh G, Mao L
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1998 Sep 15;58(18):4082-5.
Cyclin-dependent kinases can be activated by cdc25, which removes inhibitory phosphates from tyrosine and threonine residues. At least three cdc25 genes (cdc25A, cdc25B, and cdc25C) have been identified in humans. Accumulating evidence indicates that cdc25A and cdc25B possess oncogenic properties. Recently, overexpression of cdc25A and of cdc25B was found in many breast and head and neck cancers. To determine potential roles of cdc25s in non-small cell lung cancer (NSCLC), we analyzed primary tumors and corresponding normal lung tissues from 40 patients with NSCLC for relative expression levels of these genes by multiplex reverse transcription PCR (RT-PCR). cdc25A was overexpressed in 60% (24 of 40) of the tumors and cdc25B in 45% (18 of 40) of the tumors, whereas cdc25C was not overexpressed in any of the tumors analyzed. Because c-myc can increase cdc25A and cdc25B expression, it may be a factor in cdc25 overexpression. We found that c-myc was overexpressed in only 18% (7 of 40) of the tumors. We found no association between overexpression of c-myc and cdc25A or cdc25B. We also investigated whether the cdc25B gene was amplified in NSCLC and found this was true in 40% (8 of 20) of the tumors tested. However, this amplification was not correlated with gene expression status. Interestingly, among 24 tumors with cdc25A overexpression and 18 with cdc25B overexpression, 42% (10 of 24) and 44% (8 of 18) were poorly differentiated histological type. In contrast, well or moderately differentiated tumors had lower frequencies of cdc25A and cdc25B overexpression [19% (3 of 16) and 23% (5 of 22), respectively]. These data indicate that overexpression of cdc25A and cdc25B is frequent and that it may play an important role in NSCLC. However, it is unlikely that this overexpression is caused by c-myc stimulation or cdc25B gene amplification.
细胞周期蛋白依赖性激酶可被cdc25激活，cdc25能去除酪氨酸和苏氨酸残基上的抑制性磷酸基团。在人类中已鉴定出至少三种cdc25基因（cdc25A、cdc25B和cdc25C）。越来越多的证据表明cdc25A和cdc25B具有致癌特性。最近，在许多乳腺癌、头颈癌中发现了cdc25A和cdc25B的过表达。为了确定cdc25在非小细胞肺癌（NSCLC）中的潜在作用，我们通过多重逆转录PCR（RT-PCR）分析了40例NSCLC患者的原发性肿瘤及相应的正常肺组织中这些基因的相对表达水平。cdc25A在60%（40例中的24例）的肿瘤中过表达，cdc25B在45%（40例中的18例）的肿瘤中过表达，而cdc25C在所分析的任何肿瘤中均未过表达。由于c-myc可增加cdc25A和cdc25B的表达，它可能是cdc25过表达的一个因素。我们发现c-myc仅在18%（40例中的7例）的肿瘤中过表达。我们未发现c-myc过表达与cdc25A或cdc25B之间存在关联。我们还研究了cdc25B基因在NSCLC中是否扩增，发现在40%（20例检测肿瘤中的8例）的肿瘤中确实如此。然而，这种扩增与基因表达状态无关。有趣的是，在24例cdc25A过表达的肿瘤和18例cdc25B过表达的肿瘤中，42%（24例中的10例）和44%（18例中的8例）为低分化组织学类型。相比之下，高分化或中分化肿瘤中cdc25A和cdc25B过表达的频率较低[分别为19%（16例中的3例）和23%（22例中的5例）]。这些数据表明cdc25A和cdc25B的过表达很常见，且可能在NSCLC中起重要作用。然而，这种过表达不太可能是由c-myc刺激或cdc25B基因扩增引起的。
