Increased expression of centrosomal α, γ-tubulin in atypical ductal hyperplasia and carcinoma of the breast
Increased expression of centrosomal α, γ-tubulin in atypical ductal hyperplasia and carcinoma of the breast
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DOI：
10.1111/j.1349-7006.2008.01075.x
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发表时间：
2009-04-01
期刊：
影响因子：
5.7
通讯作者：
Zhang, Fei
中科院分区：
文献类型：
--
作者：
Niu, Yun;Liu, Tieju;Zhang, Fei
中心体异常已在各种癌症类型中发现。我们试图确定中心体功能障碍是否发生在乳腺癌的非典型导管增生（ADH）癌序列。由于α和γ-微管蛋白是中心体的结构成分，我们进行了真实的时间定量聚合酶链反应（qPCR），原位杂交（ISH）和免疫组织化学（IHC），以确定DNA拷贝水平，信使RNA（mRNA）表达，和α和γ-微管蛋白的蛋白质表达分别。γ-微管蛋白染色用于中心体的定位和定量。我们发现，α-微管蛋白或γ-微管蛋白的mRNA表达增加，从正常乳腺组织（NBT）ADH，导管原位癌（DCIS），浸润性导管癌（IDC），分别与最高的表达被发现在DCIS。α、γ-微管蛋白的表达谱与mRNA的表达谱一致，但在IDC中表达最高。同样，α，γ-微管蛋白的DNA拷贝数呈上升趋势，γ-微管蛋白在IDC中达到最高水平，α-微管蛋白在DCIS中发现。而α、γ-微管蛋白DNA拷贝水平、mRNA表达和蛋白表达在DCIS和IDC之间无显著差异。我们的结果表明，中心体畸变可能在乳腺肿瘤发生的早期阶段发挥关键作用。恶性转化序列可能是由于中心体DNA的扩增导致这些中心体蛋白的mRNA和蛋白质过表达。此外，使用组合的qPCR与ISH测定α，γ-微管蛋白可能有助于乳腺癌前病变的诊断。（Cancer Sci 2009; 100：580-587）
Centrosomal abnormalities have been found in various cancer types. We sought to determine whether centrosomal dysfunctions occur in the atypical ductal hyperplasia (ADH)-carcinoma sequence of breast cancer. As alpha and gamma-tubulins are the structural components of centrosomes, we performed real time quantitative polymerase chain reaction (qPCR), in situ hybridization (ISH) and immunnohistochemistry (IHC) to determine the DNA copy levels, messenger RNA (mRNA) expression, and protein expression of alpha and gamma-tubulins respectively. gamma-tubulin staining was used for the localization and quantification of centrosomes. We found that alpha-tubulin or gamma-tubulin mRNA was increasingly expressed from normal breast tissue (NBT) to ADH, ductal carcinoma in situ (DCIS), and infiltrative ductal carcinoma (IDC), respectively, with the highest expressions being found in DCIS. The expression profiles of alpha, gamma-tubulin proteins were concordant with that of mRNA, except that the highest expression was found in IDC. Similarly, DNA copies of alpha, gamma-tubulins showed a rising tendency, with the highest level for gamma-tubulin attained in IDC and that for alpha-tubulin was found in DCIS. However, there was no significant difference of alpha, gamma-tubulin DNA copy levels, mRNA expression, and protein expression between DCIS and IDC. Our results demonstrate that centrosomal aberrations may play key roles in the early stage of breast tumorogenesis. The malignant transformation sequence is probably attributable to the amplification of centrosomal DNA leading to mRNA and protein over-expression of these centrosomal proteins. Furthermore, determination of alpha, gamma-tubulins using combined qPCR with ISH may be useful in assisting the diagnosis of premalignant lesions of the breast. (Cancer Sci 2009; 100: 580-587)