Increased expression of centrosomal α, γ‐tubulin in atypical ductal hyperplasia and carcinoma of the breast

Abstract

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 α and γ‐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 α and γ‐tubulins respectively. γ‐tubulin staining was used for the localization and quantification of centrosomes. We found that α‐tubulin or γ‐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 α, γ‐tubulin proteins were concordant with that of mRNA, except that the highest expression was found in IDC. Similarly, DNA copies of α, γ‐tubulins showed a rising tendency, with the highest level for γ‐tubulin attained in IDC and that for α‐tubulin was found in DCIS. However, there was no significant difference of α, γ‐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 α, γ‐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)