December 2016 in “The journal of investigative dermatology/Journal of investigative dermatology” Hedgehog signaling controls hair follicle development and can affect skin cancer growth.
8 citations,
August 2014 in “Biochemical and Biophysical Research Communications” The study investigated the role of ornithine decarboxylase (ODC) in skin carcinogenesis by using genetically modified mice to direct ODC expression to specific epidermal compartments. It was found that K6-driven ODC over-expression in the outer root sheath of hair follicles significantly increased tumorigenesis compared to K14-driven ODC expression in inter-follicular epidermal keratinocytes. Mice with K6-ODC expression developed an average of 15 tumors per mouse, while K14-ODC mice developed 6.8 tumors per mouse. The K6-ODC mice also showed higher UVB-induced proliferation, pro-inflammatory responses, and a greater number of stem-like cells, with reduced Notch1 expression linked to stem cell expansion. The study concluded that ODC enhances tumorigenesis by negatively regulating the Notch pathway, leading to an expansion of the stem cell compartment.
64 citations,
March 2004 in “Journal of Clinical Investigation” The study demonstrated that ornithine decarboxylase (ODC) played a crucial role in the development of basal cell carcinomas (BCCs) in Ptch1+/– mice, which are predisposed to these tumors due to mutations in the patched (PTCH) gene. Overexpression of ODC in these mice accelerated BCC induction following UVB exposure, while inhibition of ODC through antizyme (AZ) overexpression or the use of the ODC inhibitor α-difluoromethylornithine reduced BCC formation. These findings suggested that targeting ODC could be an effective chemopreventive strategy for reducing BCCs in humans.
24 citations,
June 1999 in “Mechanisms of Development” The study demonstrated that ornithine decarboxylase (ODC) played a significant role in hair follicle development and hair growth by being associated with cell proliferation and commitment. ODC was expressed in embryonic epidermis at sites of follicle development and persisted in proliferating bulb cells of anagen follicles, except at the base of the bulb. Its expression decreased as follicles entered catagen and resumed with new follicle initiation. In vibrissae, ODC showed a complex expression pattern, being present in both the bulb and hair shaft, and in outer root sheath cells near the follicle bulge, suggesting a link to hair follicle stem cells.
233 citations,
July 1997 in “PubMed” In this study, researchers investigated whether overexpression of ornithine decarboxylase (ODC) was sufficient for tumor promotion in mouse skin. They used transgenic mice with high ODC expression in epidermal keratinocytes and found that these mice were more sensitive to carcinogen initiation compared to controls. Notably, mice with ODC overexpression in hair follicle keratinocytes developed tumors without the need for additional tumor promoters. The study concluded that ODC overexpression was sufficient to activate target cells in hair follicles, leading to clonal expansion and epidermal tumor formation, indicating that hair follicles are key sites for chemical carcinogen targeting in the skin.
71 citations,
May 1996 in “Journal of Investigative Dermatology” The study investigated the role of ornithine decarboxylase (ODC) in hair follicle function using transgenic mice that overexpressed a mutated ODC transgene in hair follicle keratinocytes. These mice experienced normal initial hair growth but lost their hair completely 2-3 weeks after birth, coinciding with the onset of ODC overexpression and the development of follicular cysts. The study found that the ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially restore normal skin histology if administered early, and it could also reactivate hair growth in mice with complete hair loss. The results suggested that ODC played a crucial regulatory role in mouse hair follicles.
