Centrosomal proteins和Aurora family 在人類腦瘤中的差異性表現

Abstract

Abstract The brain tumor development is different in age and tissue location, such as the meningioma, astrocytoma and metastasis tumor. The faithful distribution of the genetic material between daughter cells during cell division requires the precise segregation of duplicated chromosome and centrosome. Boveri (1914) speculated that centrosomes could contribute to chromosome missegregation and aneuploidy and this phenomenon may contribute to tumorgenesis. At 2001, Doxsey transected centrosomal protein (pericentrin) into normal prostate cell line and contribute to development of tumor-like cell line. Besides, Centrosome amplification drives chromosomal instability in breast tumor development. Furthermore, Aurora A is member of the mitotic kinase, has been shown to be localized at mitotic spindle poles and is involved in regulating centrosome maturation, chromosome segregation and maintaining genomic stability. In addition, Aurora A were found to be overexpressed in several human cancer type, such as breast cancer, colorectal cancer, blander cancer and gliomas.To gain insights into the molecular basis of the brain tumor formation, we therefore examine the differential expression of Aurora family kinase and various centrosomal proteins (including centrin, ??-tubulin and hNinein isoforms) in human brain tumor samples from KMUH medical center using reverse transcription polymerase chain reaction. Our data show that centrosomal proteins of brain tumors and cell lines display a differential expression. Interestingly, hNinein isoform 6 was only expressed in the cases of normal brain, and astrocytoma tumors (17/34), whereas it was not expressed in meningioma (0/29), metastastic tumors (0/6) and examined cell lines (1/6) except one neuroblastoma cell line. Differential expression of ??-tubulin and hNinein isoform 6 in astrocytoma is correlated to tumor grade. The data also indicate that loss of function of hNinein isoform 6 may function as a tumor-suppressor gene in astrocytomas. Further more, we use Immunofluorence staining and confocal microscopy to find that Aurora A, hNinein and ??-tubulin are shown overexpressed together with centrosome aneuploidy in glioblastoma multiform.These data suggest that centrosomal proteins, including centrin, ?n??-tubulin, hNinein isoforms and Aurora family kinase may be attributed to inappropriate centrosome behavior during various brain tumors progress.