Centrosome abnormalities in ovarian cancer

Abstract

Centrosome abnormalities have been found in various cancer types and are thought to be involved in early development of cancer and/or progression. The contribution of centrosome abnormalities to ovarian tumorigenesis has not been previously evaluated. We sought to determine whether centrosome dysfunction occurs in ovarian tumorigenesis, and whether it could be used as an indicator of early neoplastic changes in ovarian surface epithelium (OSE). Primary cultures of normal OSE and ovarian tumors, as well as paraffin-embedded normal ovaries and ovarian tumors of different stages, were used for immunostaining with a ␥-tubulin antibody. Centrosomes were considered abnormal if there were more than 2 per cell, if their sizes were greater than 2-fold of a normal centrosome, and/or if they were abnormal in shape. Centrosomes in normal tissue were uniform in size, whereas centrosomes in ovarian tumors tended to be abnormal in size, number and shape. On average, 4.7% of cells in 5 primary normal OSE cultures had more than 2 centrosomes, whereas 14.1% of primary cells from 5 ovarian tumors displayed centrosome abnormalities (p ‫؍‬ 0.008). Centrosome abnormalities were present in 60.9% of stage I (n ‫؍‬ 23), 83.3% of stage II (n ‫؍‬ 30) and all stage III (n ‫؍‬ 10) paraffin-embedded ovarian tumor samples examined, but not in normal tissues. In addition, centrosome abnormalities occurred more frequently in ovarian tumors with higher grade and aggressive serous subtype. This is the first demonstration that centrosome abnormalities occur in ovarian tumors. Centrosome dysfunction may be an early event in ovarian carcinogenesis and involved in ovarian tumor progression.

Application of Bayesian Modeling of Autologous Antibody Responses against Ovarian Tumor-Associated Antigens to Cancer Detection

“…Intriguingly, disruption of the centrosomes is an early event in the genesis of ovarian cancer. Furthermore, the breast and ovarian cancer hereditary susceptibility genes BRCA1 and BRCA2 contribute to a centrosome function that is believed to help maintain the integrity of the chromosome segregation process (50,51).…”

Differential regulation of centrosome integrity by DNA damage response proteins

“…Centrosome amplification in conjunction with mitotic spindle abnormalities correlates with genomic instability and malignancy during tumor progression in several cancer types, including breast cancer. [37][38][39] We therefore sought to examine whether the status of MDC1 or BRIT1 was linked to centrosome amplification and mitotic defects in breast cancer specimens. By immunohistochemical analysis, we found that, compared with MDC1 levels in adjacent normal breast tissue, MDC1 expression was significantly decreased in 50% of breast cancer specimens (5 of 10) (Fig.…”

The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells

“…Cell lines and cell culture Human ovarian cancer cells SKOV3 (Akt constitutively active and p53 homozygously mutated) and ES2 (Akt inactive and one allele of p53 mutated) (Concin et al 2003;El-Gazzar et al 2010), purchased from ATCC (Manassas, VA, USA), were grown in McCoy's 5A medium supplemented with 10 % fetal bovine serum and 1.5 mM L-glutamine at 37°C in a humidified 5 % CO 2 atmosphere. Normal ovarian surface epithelial cells were cultured in MCDB105/medium 199 (1:1) supplemented with 15 % fetal bovine serum, 2 mM L-glutamine and penicillin/streptomycin (Hsu et al 2005).…”