Centrosomeγ-tubulin, Nek2and Chromosomal Abnormality Associated With Pathogenesis Of Breast Cancer

Purpose This study is to analyze the change of the centrosome γ-tubulin and itsregulatory factor Nek2at the subcellular,, molecular and genetic level in variousstages of the mammary epithelial malignant process. This will help us to understandthe mechanism of breast cancer evolution and provides information for selecting thetarget of gene therapy for precancerous lesions and early infiltrate cancer.Methods Six groups and210samples of breast tissues were collected from normaltissue, atypical hyperplasia, high-and low-grade ductal carcinoma in situ, and high-and low-grades of invasive ductal carcinoma. Immunohistochemistry and flowcytometry immuno fluorescence techniques were used to detect centrosomeγ-tubulin and the Nek2protein expression. Digoxin labeled mRNA in situhybridization and real-time quantitative reverse transcription PCR techniques wereused to detect γ-tubulin and Nek2mRNA expression levels. Comparative genomichybridization was used to detect of the gain and loss of chromosomal DNA copynumbers well as chromosomal abnormalities.Results From development process of normal breast, atypical hyperplasia, ductalcarcinoma in situ, to invasive ductal carcinoma, the expression of mRNA andprotein of centrosome γ-tubulin and Nek2were significantly up regulated. Therewas no significant difference between the levels of γ-tubulin and Nek2expression.The γ-tubulin and Nek2expression in the DNA aneuploid group were significantlyhigher than those in the diploid group. Higher the γ-tubulin expression is, andbigger the abnormal changes of chromosomal DNA is. Compared to the normaltissue samples, a majority of atypical hyperplasia samples showed a higher levelprotein and mRNA expression of γ-tubulin and Nek2, but the low-grade cancer didnot; Average gain and loss of chromosomes in the low-grade of cancer weresignificantly lower than those in the high-grade cancer, but no significantdifferences was observed between carcinoma in situ and low-grade invasivecarcinoma. Chromosomal abnormality of the atypical hyperplasia was significantlyhigher than that of the cancer tissue. High-grade carcinoma in situ and invasivecancer have the same chromosomal and locus cytogenetic abnormalities with manycommon deletion. Conclusion Abnormal protein and mRNA expression of centrosome γ-tubulin andNek2may play an important role in the successive proliferation of the malignanttransformation process to breast cells. γ-tubulin and Nek2may be the target of genetherapy in early invasive cancer. Cytogenetic histological changes occur prior tomorphological changes in atypical hyperplasia, which may have close genetic tieswith low-grade cancer and may be potential cancer precursor lesions. Low-gradecancer and high-grade cancer have different molecular and genetic alterations, andthey may have their own pathes to progress.