Expression of the mitotic-arrest deficiency 2 is associated with chemotherapy resistance in ovarian serous adenocarcinoma

Abstract

Mitotic-arrest deficiency 2 (MAD2) is a key component of spindle assembly checkpoint (SAC) function; SAC mediates spindle microtubule attachment to kinetochores on chromosomes and chromosomal segregation during mitosis. To determine whether MAD2 expression is associated with chemotherapy resistance in ovarian serous adenocarcinoma, we reviewed tumor samples from 41 cases of ovarian serous adenocarcinoma at Osaka City University Medical School Hospital (Osaka, Japan), 2000-2007. Of the 41 cases, 24 were recurrent and 17 were not recurrent. Expression of MAD2 was investigated in paraffin-embedded sections using a MAD2 antibody. Quantitative analysis of MAD2 expression gave mean weighted scores of 4.3 for the relapsed group and 7.2 for the relapse-free group; the expression was, thus, significantly greater in the relapse-free group compared to the relapsed group (P=0.023). When the 41 cases were classified into low- and high-expression, these classifications showed no significant difference in terms of progression-free survival (P=0.0685), however, overall survival for the low-expression group was significantly shorter than that of the high-expression group (P=0.0188). The present study implies that MAD2 expression levels can indicate sensitivity to anticancer agents, and risk for recurrence.

DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation

“…CENPN is required to recruit the Mad2 SAC protein to prometaphase kinetochores [24]. MAD2 is a key component of the mitotic spindle checkpoint pathway, and MAD2 overexpression is observed in several cancers [25]. MAD2 overexpression in transgenic mice notably results in chromosomal instability and initiates carcinogenesis in a wide variety of tumors [26].…”

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.…”

Identification of Hub Genes in High-Grade Serous Ovarian Cancer Using Weighted Gene Co-Expression Network Analysis

“…As a component of the mitotic checkpoint, high levels of MAD2L1 are related to increased cellular proliferation, migration, and metastasis, which can lead to shorter survival in various cancers [22][23][24][25][26]. However, in ovarian cancer, the role of MAD2L1 did not agree with previous findings that patients with lower MAD2L1 levels were less sensitive to paclitaxel and had shorter progression-free survival (PFS) and overall survival (OS) [27,28]. This discrepancy might have been caused by our analysis, ignoring the mutations of p53 and BRCA1, which are known regulators of MAD2L1 and are commonly mutated in HGSOC [29,30].…”