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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

eQTL map of Egfr based on the whole genome expression profiles of the liver of the female population. A. EQTL map of whole genome showing the loci on chromosome 5, 6, and 18. B. The peak region of eQTL on chromosome 5. C. Gene network of 12 candidate genes of eQTL on chromosome 5 and Egfr derived from the liver of the female mice. The 13 nodes in the graph below show the selected traits. All the nodes are displayed. The 15 edges between the nodes, filtered from the 78 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.3 or less than -0.3. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 16.0 point font, and the edge labels are drawn with a 16.0 point font.
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Figure 6: eQTL map of Egfr based on the whole genome expression profiles of the liver of the female population. A. EQTL map of whole genome showing the loci on chromosome 5, 6, and 18. B. The peak region of eQTL on chromosome 5. C. Gene network of 12 candidate genes of eQTL on chromosome 5 and Egfr derived from the liver of the female mice. The 13 nodes in the graph below show the selected traits. All the nodes are displayed. The 15 edges between the nodes, filtered from the 78 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.3 or less than -0.3. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 16.0 point font, and the edge labels are drawn with a 16.0 point font.

Mentions: We finally examined the genetic factors that regulate the expression of Egfr in the livers of female and male mice. With 5000 permutation test, we detected eQTLs for the regulation of Egfr from female liver on chromosome 5 and 6 (Figure 6A). The eQTL on chromosome 5 is significant. The significant threshold is 18.48, and the suggestive threshold is 10.87. The eQTL on chromosome 5 reached the level of 19. We did not detect an eQTL on either chromosome 5 or 6 from the data of male liver. The eQTL for male mice are on chromosome 7 and 8, but all suggestive. Thus, the level of Egfr expression is differently regulated between male and female mice.


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)

eQTL map of Egfr based on the whole genome expression profiles of the liver of the female population. A. EQTL map of whole genome showing the loci on chromosome 5, 6, and 18. B. The peak region of eQTL on chromosome 5. C. Gene network of 12 candidate genes of eQTL on chromosome 5 and Egfr derived from the liver of the female mice. The 13 nodes in the graph below show the selected traits. All the nodes are displayed. The 15 edges between the nodes, filtered from the 78 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.3 or less than -0.3. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 16.0 point font, and the edge labels are drawn with a 16.0 point font.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4829553&req=5

Figure 6: eQTL map of Egfr based on the whole genome expression profiles of the liver of the female population. A. EQTL map of whole genome showing the loci on chromosome 5, 6, and 18. B. The peak region of eQTL on chromosome 5. C. Gene network of 12 candidate genes of eQTL on chromosome 5 and Egfr derived from the liver of the female mice. The 13 nodes in the graph below show the selected traits. All the nodes are displayed. The 15 edges between the nodes, filtered from the 78 total edges and drawn as curves, show Pearson correlation coefficients greater than 0.3 or less than -0.3. The graph's canvas is 40.0 by 40.0 cm; the node labels are drawn with a 16.0 point font, and the edge labels are drawn with a 16.0 point font.
Mentions: We finally examined the genetic factors that regulate the expression of Egfr in the livers of female and male mice. With 5000 permutation test, we detected eQTLs for the regulation of Egfr from female liver on chromosome 5 and 6 (Figure 6A). The eQTL on chromosome 5 is significant. The significant threshold is 18.48, and the suggestive threshold is 10.87. The eQTL on chromosome 5 reached the level of 19. We did not detect an eQTL on either chromosome 5 or 6 from the data of male liver. The eQTL for male mice are on chromosome 7 and 8, but all suggestive. Thus, the level of Egfr expression is differently regulated between male and female mice.

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