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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression

Department of Biomolecular Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
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Author to whom correspondence should be addressed.
Biomolecules 2020, 10(4), 545; https://doi.org/10.3390/biom10040545
Received: 6 March 2020 / Revised: 1 April 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
(This article belongs to the Special Issue MAPKs in Skin Health and Disease)
An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin. View Full-Text
Keywords: aquaporin-3; dry skin; erlotinib; EGFR; ERK aquaporin-3; dry skin; erlotinib; EGFR; ERK
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MDPI and ACS Style

Ikarashi, N.; Kaneko, M.; Watanabe, T.; Kon, R.; Yoshino, M.; Yokoyama, T.; Tanaka, R.; Takayama, N.; Sakai, H.; Kamei, J. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression. Biomolecules 2020, 10, 545. https://doi.org/10.3390/biom10040545

AMA Style

Ikarashi N, Kaneko M, Watanabe T, Kon R, Yoshino M, Yokoyama T, Tanaka R, Takayama N, Sakai H, Kamei J. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression. Biomolecules. 2020; 10(4):545. https://doi.org/10.3390/biom10040545

Chicago/Turabian Style

Ikarashi, Nobutomo, Miho Kaneko, Tomofumi Watanabe, Risako Kon, Makana Yoshino, Takatoshi Yokoyama, Riho Tanaka, Naoya Takayama, Hiroyasu Sakai, and Junzo Kamei. 2020. "Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Induces Dry Skin via Decreased in Aquaporin-3 Expression" Biomolecules 10, no. 4: 545. https://doi.org/10.3390/biom10040545

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