Abstract
Human fragile WWOX gene encodes a candidate tumor suppressor WW domain‐containing oxidoreductase. Previous studies have shown that ectopically overexpressed WWOX induces apoptosis in cancer cells and suppresses tumor growth both in vitro and in vivo. Functional suppression of WWOX by antisense mRNA, dominant negatives, and small interfering RNA protects cells from apoptosis by tumor necrosis factor, anticancer drugs, UV light, and ectopic p53 in vitro. Interestingly, substantial evidence revealed that progression of various cancers to a pre‐metastatic stage positively correlates with upregulation of WWOX protein expression, suggesting that WWOX may act more than a tumor suppressor. In normal human epidermis, WWOX is abundant in proliferating epithelial cells of the skin, and its expression is increased in intensity toward the superficial layers. In this study, we determined a reduced number of Ki67‐positive proliferating keratinocytes in the epidermis of our newly developed Wwox gene knockout (Wwox−/−) mice. A marked reduction in the basal (K5‐positive) and suprabasal (K10‐positive) keratinocyte numbers was examined in the keratinized squamous epithelium of the Wwox−/− mouse skin. Apparent decreases in Wwox−/− epidermal and dermal thickness were found. To further verify whether WWOX regulates keratinocyte growth, we detected significantly decreased cell proliferation in both ex vivo Wwox−/− primary keratinocyte cultures and WWOX‐knockdown HaCaT cells as compared to the controls. No significant increase in the number of TUNEL‐positive cells was observed in the Wwox−/− epidermis. Moreover, our recent data showed that keratinocyte differentiation was slightly enhanced in WWOX‐knockdown HaCaT cells. Together, our results clearly demonstrated a crucial role of WWOX in regulating normal keratinocyte proliferation for maintaining skin homeostasis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call