Anti-EREG monoclonal antibody, clone 294736

Gene expression during oocyte maturation and early embryogenesis up to zygotic genome activation requires translational activation of maternally-derived mRNAs. EPAB [embryonic poly(A)-binding protein] is the predominant poly(A)-binding protein during this period in Xenopus, mouse and human. In Xenopus oocytes, ePAB stabilizes maternal mRNAs and promotes their translation. To assess the role of EPAB in mammalian reproduction, we generated Epab-knockout mice. Although Epab(-/-) males and Epab(+/-) of both sexes were fertile, Epab(-/-) female mice were infertile, and could not generate embryos or mature oocytes in vivo or in vitro. Epab(-/-) oocytes failed to achieve translational activation of maternally-stored mRNAs upon stimulation of oocyte maturation, including Ccnb1 (cyclin B1) and Dazl (deleted in azoospermia-like) mRNAs. Microinjection of Epab mRNA into Epab(-/-) germinal vesicle stage oocytes did not rescue maturation, suggesting that EPAB is also required for earlier stages of oogenesis. In addition, late antral follicles in the ovaries of Epab(-/-) mice exhibited impaired cumulus expansion, and a 8-fold decrease in ovulation, associated with a significant down-regulation of mRNAs encoding the EGF (epidermal growth factor)-like growth factors Areg (amphiregulin), Ereg (epiregulin) and Btc (betacellulin), and their downstream regulators, Ptgs2 (prostaglandin synthase 2), Has2 (hyaluronan synthase 2) and Tnfaip6 (tumour necrosis factor alpha-induced protein 6). The findings from the present study indicate that EPAB is necessary for oogenesis, folliculogenesis and female fertility in mice.

Background/Aim:A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer.Methods:We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS).Results:High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2,p= 0.047 andp< 0.001), pre-Tx and post-Tx negative nodal status (N0,p< 0.001 andp= 0.004), less vascular and perineurial invasion (p= 0.015 andp= 0.023), and higher tumor regression grade (p< 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p< 0.0001), LRFS (p= 0.0004), and MeFS (p< 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p= 0.003; hazard ratio: 5.599).Conclusion:These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.