Sex difference in EGFR pathways in mouse kidney-potential impact on the immune system

Abstract

BackgroundEpidermal growth factor receptor (Egfr) has been the target of several drugs for cancers. The potential gender differences in genes in the Egfr axis have been suggested in humans and in animal models. Female and male mice from the same recombinant inbred (RI) strain have the same genomic components except the sex difference. A population of different RI mouse strains allows to conduct precise analysis of molecular pathways and regulation of Egfr between female and male mice.MethodsThe whole genome expression profiles of 70 genetically diverse RI strains of mice were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and expression quantitative trait loci (eQTL) that regulate the expression of Egfr between female and male mice.ResultsOur data showed that there is a significant sex difference in the expression levels in kidney. A considerable number of genes in the gene network of Egfr are sex differentially expressed. The expression levels of Egfr in mice are statistical significant different between C57BL/6 J (B6) and DBA/2 J (D2) genotypes in male while no difference in female mice. The eQTLs that regulate the expression levels of Egfr between female and male mice are also different. Furthermore, the differential expression levels of Egfr showed significantly different correlations with two known biological traits between male and female mice.ConclusionOverall there is a substantial sex difference in the Egfr pathways in mice. These data may have significant impact on drug target design, development, formulation, and dosage determinant for women and men in clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0449-3) contains supplementary material, which is available to authorized users.

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma

“…In the gender subgroup analysis of the current study, the female EGFR mutation population showed a higher distribution frequency of LncRNA H19 SNP rs217727 as well as rs2107425 but a lower distribution frequency of LncRNA H19 SNP rs2839698. The difference of LncRNA H19 SNP distribution between the two gender subgroups may be due to the existence of expression quantitative trait loci which lead to gender-difference expression of LncRNA inter chr4 3011 in mice [ 46 ] and the possible difference function of EGFR pathway between gender, which is found in the kidney mouse [ 47 ], may also cause such gender difference as the expression of LncRNA PACER in periodontitis [ 48 ]. Since the LncRNA H19 SNP rs217727 was related to lung cancer development [ 45 ] and LncRNA H19 SNP rs2107425 was correlated to shorter metastasis-free survival [ 49 ], it may be reasonable for the similar condition in the current study.…”

Gender differences in colorectal cancer survival: A meta‐analysis

“…[3][4][5] It has been reported that there are differences in the molecular pathways of EGFR in the kidney and liver between female and male mice. Most importantly, NRP1 is the co-receptor of epidermal growth factor receptor (EGFR), which can control EGFR signaling and tumor growth.…”

“…Most importantly, NRP1 is the co-receptor of epidermal growth factor receptor (EGFR), which can control EGFR signaling and tumor growth. [3][4][5] It has been reported that there are differences in the molecular pathways of EGFR in the kidney and liver between female and male mice. Many of sex differential expressed genes are related to hormone metabolism.…”

“…This study demonstrated that gender difference in drug targeting EGFR may have influence on the treatment and prognosis of colorectal cancer patients with liver and kidney metastasis, but further clinical trials are needed. 3,6 Survival after colorectal cancer resection is mainly adjusted for patient characteristics, cancer progression and medical treatment. A study has identified disparities not only in survival, but also in patterns of presentation, surgical resection, and treatment regimens between women and men that could serve as targets for quality improvement.…”

Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors

“…Interestingly, P-EGF-Cy7 did not exhibit any significant tumor accumulation, while in vitro results showed a relatively strong interaction with EGFR. However, a strong accumulation of P-EGF-Cy7 in liver and kidney was observed at all time intervals, which may be due to the cross-reactivity of the human EGF [27] with murine EGFR overexpressed in liver [28] and kidney of mice [29]. No significant accumulation of GE11 and mAb cetuximab in liver and kidney was observed, thus proving no or very low cross-reactivity with mouse EGFR.…”