17 citations,
July 2013 in “Amino Acids” Elevated ornithine decarboxylase (ODC) activity in the epidermis was found to promote skin tumor development by recruiting hair follicle bulge stem cells, as demonstrated in ODC-ER transgenic mice. The study showed that inducing ODC activity with 4-hydroxytamoxifen (4OHT) was sufficient to recruit these stem cells in quiescent skin. Although increased ODC activity also led to higher reactive oxygen species (ROS) generation, the use of the polyamine catabolic oxidase inhibitor MDL72527 revealed that ROS generation did not contribute to tumorigenesis. Instead, MDL72527 treatment resulted in a shorter tumor latency, increased tumor burden, and more carcinomas, indicating that the recruitment of bulge stem cells, rather than ROS, played a key role in tumor promotion.
61 citations,
July 2011 in “PLOS ONE” Spermidine may help reduce hair loss and deserves further testing as a treatment.
1039 citations,
February 2009 in “Nature Reviews Molecular Cell Biology” Skin stem cells are crucial for maintaining and repairing the skin and hair, using a complex mix of signals to do so.
37 citations,
January 2006 in “Carcinogenesis” The study tested whether suppressing ornithine decarboxylase (ODC) activity could block skin tumor promotion in mice with activated MEK mutations. By crossing these mice with those overexpressing antizyme (AZ), which degrades ODC, researchers found that AZ expression significantly delayed tumor development and reduced tumor numbers. This effect was most pronounced in MEK/K6-AZ mice, which had fewer than one tumor per mouse after 8 weeks, compared to over 13 tumors in MEK-only mice. The study suggested that AZ primarily inhibited putrescine accumulation, slowing cell growth by increasing G2/M transit time, without inducing apoptosis.
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.
65 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 PTCH gene. Overexpression of ODC in these mice accelerated BCC induction following UVB exposure, while inhibition of ODC through antizyme overexpression or oral administration of the ODC inhibitor α-difluoromethylornithine reduced BCC formation. These findings suggested that targeting ODC could be an effective chemopreventive strategy against BCCs in humans.
67 citations,
September 2001 in “American Journal Of Pathology” Inhibiting ODC can prevent UV-induced skin cancer.
20 citations,
April 2000 in “Experimental dermatology” ODC transgenic mice can model human hair loss with skin lesions.
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.
