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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.

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.

The study investigated the effects of dexamethasone (DXME) on mouse skin treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). DXME, when applied after TPA, inhibited both the dermal inflammatory reaction and the induction of epidermal ornithine decarboxylase (ODC) activity. During the hyperplastic stage, DXME continued to counteract inflammation but only weakly inhibited ODC induction. Interestingly, in DXME-protected skin, the hyperplastic stage was delayed, and TPA strongly induced ODC activity in the epidermal cell layer before this stage. The study suggested that as the proliferation process was induced, epidermal cells became more sensitive to TPA, potentially becoming less reliant on inflammatory factors for ODC induction.