Mitotic arrest deficiency 2 induces carcinogenesis in mucinous ovarian tumors

Abstract

Abstract. Mitotic arrest deficiency 2 (MAD2) is a key component of the mitotic spindle checkpoint pathway. A compromised mitotic spindle checkpoint results in an abnormal number of chromosomes. This is referred to as chromosomal instability, and has been reported in most types of human cancer. The aim of this study was to examine the expression of MAD2 in mucinous ovarian tumors exhibiting varying degrees of malignancy. We reviewed 128 cases of mucinous ovarian tumors initially treated at Osaka City University Medical School Hospital, Japan. Tumor samples were obtained following surgery. The cases were divided into three groups: benign (group B; n=30), borderline malignant (group BM; n=55) and malignant (group M; n=43). MAD2 expression was examined in paraffin-embedded sections using the avidin-biotin peroxidase complex method. Results showed MAD2 expression to be significantly greater in group M compared to groups B and BM (P<0.05). In addition, there was a moderate correlation between MAD2 expression and the degree of malignancy (r=0.51, P<0.05). However, when the samples in group M were classified according to a low or high expression of MAD2, no difference was observed in terms of overall survival. These findings suggest that the overexpression of MAD2 may be correlated to carcinogenesis in mucinous ovarian tumors.

Mechanisms of Taxane Resistance

“…BUBR1 and MAD2 directly prevent activation of the Anaphase-Promoting Complex (APC/c) by binding to CDC20 and maintaining a closed confirmation [ 210 ]. Using siRNA to silence MAD2, PTX-induced apoptosis was reduced and demonstrated that MAD2 levels play a definite role in the SAC signal, mitotic arrest, and arrest-induced apoptosis [ 211 , 212 , 213 ]. Moreover, decreased levels of MAD2 have even been hypothesized to be a factor in tumorigenesis in mucinous OC [ 214 ], suggesting that MAD2 is more of a driving factor in cell proliferation and disease progression than any other SAC-related protein.…”

The association between MAD2 and prognosis in cancer: a systematic review and meta-analyses

“…Another limitation is that a meta-analysis for cancer-specific survival according to MAD2 expression was unable to be undertaken due to a lack of studies reporting on this outcome. Also the majority of the studies utilised in this review were unadjusted for confounders known to affect survival of cancer patients such as age and stage [ 60 , 61 ]. It is therefore difficult to determine how age and stage would affect the association of MAD2 expression on patient survival [ 62 – 64 ].…”

Structure–Biological Function Relationship Extended to Mitotic Arrest-Deficient 2-Like Protein Mad2 Native and Mutants-New Opportunity for Genetic Disorder Control

“…Initial methods described proteins solvent accessible surface area as the surface “probed” by the center of a water probe sphere with a radius of 1.4 Å as it rolls over the van der Waals surface of the molecule, while a polyhedral representation is used for each atom in calculating the surface area. Since proteins contain huge number of hydrophobic and polar atoms, each of them with acceptor/donor of hydrogen bonds features, the above-mentioned limitations of computational methods performed on the global proteins surface [ 35 ] apply here. Taking this fact into account, we considered that the prediction accuracy of protein-protein interactions could be significantly improved if we performed an individual calculation on subdivided molecular surfaces segregated by types of atoms.…”