Gene Amplification and Overexpression of Aurora-C in Breast and Prostate Cancer Cell Lines

Abstract

Human aurora kinases are three highly conserved serine/threonine kinases with regulatory function in chromosome alignment, chromosome segregation, and cytokinesis during cell cycle progression and their overexpression associates with malignant transformation and proliferation of cancer cells. Aurora genes are located at loci that are commonly altered in cancers. Aurora-A has oncogenic activity while Aurora-B does not. Aurora-C is only detected in mammals with involvement in meiosis. Oncogenic activity of Aurora-C is still in dispute. We evaluated the expression of three Aurora kinases by real-time RT-PCR in well-known breast and prostate cancer cell lines. Cell cycle was studied with flow cytometry. In both more invasive cell lines' p53-null cells, PC-3 and MDA-MB-231, an increase in mRNA expression of three Aurora kinases, especially Aurora-C, was observed. Genomic DNA was examined for gene amplification and aneuploidy as a mechanism of overexpression. At DNA level, only Aurora-C showed gene amplification in breast cancer cell lines (p < 0.005). Here we provide evidence for the first time of Aurora-C overexpression and gene amplification.

Aurora kinases: novel therapy targets in cancers

“…Chromosome mis-segregation during meiosis due to aberrant AURKC expression or activity leads to aneuploidy in gametes, causing genetic infertility [90]. AURKC may promote tumor development in view of overlapping and complementary function with AURKB, as well as gene amplification and overexpression in cancers [11] though the mechanism is still in dispute.…”

“…Loss of AURKB activity could override spindle assembly checkpoint (SAC) through premature removal of SAC proteins from the kinetochore [7], which leads to defect of chromosome segregation and conformation of polyploidy. Overexpression or amplification of Aurora kinases is generally detected in amount of human cancers, such as breast cancer [8–11], ovarian cancer [12–14], gastric/gastrointestinal cancer [15, 16] and other tumors [11, 17–33] (Table 1) and is associated with the poor prognosis [8, 34, 35]. Thus, Aurora kinases become promising therapeutic targets and numerous AKIs have been developed.…”

The aurora kinases in cell cycle and leukemia

“…Aurora C is aberrantly expressed in cancer cell lines 94 . One study showed that its overexpression induced abnormal cell division resulting in centrosome amplification, multinucleation and increased proliferation 95 .…”

Overexpression of Aurora-C interferes with the spindle checkpoint by promoting the degradation of Aurora-B

“…9 However, increasing evidence indicates that Aurora-C is also overexpressed in numerous somatic cancer tissues and hematologic cancers. 10, 11, 12, 13 Our previous report indicated that overexpressed Aurora-C can promote the tumorigenicity of cancer cells. 14 The aberrant expression of Aurora-C is positively correlated with tumor progression in human cervical cancer and colorectal cancer.…”