NuMA Overexpression in Epithelial Ovarian Cancer

Abstract

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon.NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC) and immunofluorescence (IF), with results correlated to associated clinical data. Aneuploidy status in primary cultures was determined by FACS analysis.Affymetrix microarray data indicated that NuMA was overexpressed in tumour tissue, primary cultures and cell lines compared to normal ovarian tissue. IHC revealed low to weak NuMA expression in normal tissues. Expression was upregulated in tumours, with a significant association with disease stage in mucinous EOC subtypes (p = 0.009), lymph node involvement (p = 0.03) and patient age (p = 0.04). Additional discontinuous data analysis revealed that high NuMA levels in tumours decreased with grade (p = 0.02) but increased with disease stage (p = 0.04) in serous EOC. NuMA expression decreased in late disease stage 4 endometrioid EOCs. High NuMA levels decreased with increased tumour invasion in all subtypes (p = 0.03). IF of primary cultures revealed that high NuMA levels at mitotic spindle poles were significantly associated with a decreased proportion of cells in cytokinesis (p = 0.05), increased binucleation (p = 0.021) and multinucleation (p = 0.007), and aneuploidy (p = 0.008).NuMA is highly expressed in EOC tumours and high NuMA levels correlate with increases in mitotic defects and aneuploidy in primary cultures.

The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice

“…Interestingly, these genes have all been associated with cancer risk. For example, mutations in ARHA1 ( RHOA ) have been repeatedly associated with risk of diffuse gastric cancer [45;46]; NUMA over expression has been significantly associated with disease stage and local metastases to lymph nodes in ovarian cancer [47]; and LCN2 , after the activation of the PI3/AKT/NFkB [48], has been shown to form complexes with MMP9 and these, in turn, being associated with reduced survival in gastric cancer [49;50]. Since progression to more advanced gastric lesions may be associated with the development of gastric cancer, and because previous studies had suggested that CD44 may be a marker of advanced gastric lesions [34;35], we wanted to investigate the role of this gene in development of gastric lesions.…”

Fate of iPSCs Derived from Azoospermic and Fertile Men following Xenotransplantation to Murine Seminiferous Tubules

“…In parallel, we also performed immunohistochemistry in cross sections of testes transplanted with human fetal testis cells. In order to detect all human donor cells in recipient testes, we assessed expression of NuMA (Figure 3D), a well-characterized protein that exclusively labels human cells and tissues (Abad et al, 2007; Bruning-Richardson et al, 2012; Saadai et al, 2013). We observed significant human germ cell engraftment eight weeks post-transplantation (Figure 3C, iii).…”

Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules

“…Indeed, a recent study showed that NuMA is over‐expressed in human epithelial ovarian cancer (Bruning‐Richardson et al . ). As the pRB/pRB pathway was also shown to be altered in human high‐grade serous epithelial ovarian cancer (Szabova et al .…”