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Sex Difference of Egfr Expression and Molecular Pathway in the Liver: Impact on Drug Design and Cancer Treatments?

Wang L, Xiao J, Gu W, Chen H - J Cancer (2016)

Bottom Line: Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice.Several important genes in the gene network of Egfr are differentially expressed between female and male mice.The regulatory elements for the expression levels of Egfr between female and male mice are also different.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.; 2. Department of Basic Medical Research, Inner Mongolia Medical University, Inner Mongolia, 010110, China.

ABSTRACT
Epidermal growth factor receptor (EGFR) has been used as the target in drug design for cancer treatment including the liver cancer. Men and women have different levels of EGFR expression during the life. The whole genome expression profiles of livers of recombinant inbred (RI) strains derived from C57BL/6J (B6) X DBA/2J (D2) were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and eQTLs that regulate the expression of Egfr between female and male mice. Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice. Several important genes in the gene network of Egfr are differentially expressed between female and male mice. The regulatory elements for the expression levels of Egfr between female and male mice are also different. In summary, our data reveals an important sex difference in the Egfr pathways in the liver of the mice. These data may have substantial impact on drug development and dosage determinant for women and men in the clinical trials.

No MeSH data available.


Related in: MedlinePlus

Gene network of top 50 genes that are closely associated to Egfr in the male mouse liver and their network in the female liver. The 50 nodes in the graph below show the selected traits. Only nodes with the edges are displayed. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 18.0 point font, and the edge labels are drawn with a 18.0 point font. A. Gene network in the female liver. The 684 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5. B. Gen network in the liver of the male mice. The 366 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5.
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Figure 3: Gene network of top 50 genes that are closely associated to Egfr in the male mouse liver and their network in the female liver. The 50 nodes in the graph below show the selected traits. Only nodes with the edges are displayed. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 18.0 point font, and the edge labels are drawn with a 18.0 point font. A. Gene network in the female liver. The 684 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5. B. Gen network in the liver of the male mice. The 366 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5.

Mentions: As shown in Figure 3A, Egfr is positively and negatively correlated to several genes in the female mice. The expression of mouse Egfr is strongly positively correlated to translocating chain-associating membrane protein 1 (Tram1), RIKEN cDNA 1190006C12 gene (for Sec61b); Both Tram1 and Sec61b then have strong connections to multiple genes. Egfr is strongly negatively correlated to dedicator of cytosolic acyl-CoA thioesterase 1 (Cte1). Cte1 has negative impact on several other genes.


Sex Difference of Egfr Expression and Molecular Pathway in the Liver: Impact on Drug Design and Cancer Treatments?

Wang L, Xiao J, Gu W, Chen H - J Cancer (2016)

Gene network of top 50 genes that are closely associated to Egfr in the male mouse liver and their network in the female liver. The 50 nodes in the graph below show the selected traits. Only nodes with the edges are displayed. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 18.0 point font, and the edge labels are drawn with a 18.0 point font. A. Gene network in the female liver. The 684 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5. B. Gen network in the liver of the male mice. The 366 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4829553&req=5

Figure 3: Gene network of top 50 genes that are closely associated to Egfr in the male mouse liver and their network in the female liver. The 50 nodes in the graph below show the selected traits. Only nodes with the edges are displayed. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 18.0 point font, and the edge labels are drawn with a 18.0 point font. A. Gene network in the female liver. The 684 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5. B. Gen network in the liver of the male mice. The 366 edges between the nodes, filtered from the 1225 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.5 or less than -0.5.
Mentions: As shown in Figure 3A, Egfr is positively and negatively correlated to several genes in the female mice. The expression of mouse Egfr is strongly positively correlated to translocating chain-associating membrane protein 1 (Tram1), RIKEN cDNA 1190006C12 gene (for Sec61b); Both Tram1 and Sec61b then have strong connections to multiple genes. Egfr is strongly negatively correlated to dedicator of cytosolic acyl-CoA thioesterase 1 (Cte1). Cte1 has negative impact on several other genes.

Bottom Line: Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice.Several important genes in the gene network of Egfr are differentially expressed between female and male mice.The regulatory elements for the expression levels of Egfr between female and male mice are also different.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.; 2. Department of Basic Medical Research, Inner Mongolia Medical University, Inner Mongolia, 010110, China.

ABSTRACT
Epidermal growth factor receptor (EGFR) has been used as the target in drug design for cancer treatment including the liver cancer. Men and women have different levels of EGFR expression during the life. The whole genome expression profiles of livers of recombinant inbred (RI) strains derived from C57BL/6J (B6) X DBA/2J (D2) were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and eQTLs that regulate the expression of Egfr between female and male mice. Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice. Several important genes in the gene network of Egfr are differentially expressed between female and male mice. The regulatory elements for the expression levels of Egfr between female and male mice are also different. In summary, our data reveals an important sex difference in the Egfr pathways in the liver of the mice. These data may have substantial impact on drug development and dosage determinant for women and men in the clinical trials.

No MeSH data available.


Related in: MedlinePlus