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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.

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.

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.

The study explored the impact of ornithine decarboxylase (ODC) overexpression on protein kinase CK2 activity in Balb/MK cells and K6/ODC transgenic mice, revealing that increased ODC expression elevated polyamine levels, which enhanced CK2 activity and caused its translocation to the nucleus. This suggested that polyamines regulated CK2 by affecting its distribution and activity, potentially contributing to tumor development. The use of an ODC inhibitor reduced polyamine levels and CK2 activity, supporting the regulatory role of polyamines. Despite increased CK2 protein levels, the rise in enzyme activity was modest, indicating a complex relationship between protein levels and activity.

This study found that the Odc1 gene, which encodes ornithine decarboxylase (ODC), was directly regulated by the androgen receptor (AR) in skeletal muscle myoblasts and played a role in myoblast proliferation and differentiation. Odc1 expression was significantly reduced in muscle from male muscle-specific AR knockout mice, indicating its regulation by AR. In vitro experiments showed that Odc1 expression was higher in proliferating myoblasts compared to differentiated myotubes, and dihydrotestosterone increased Odc1 levels in myoblasts. Inhibition of ODC activity reduced myoblast numbers, while overexpression of Odc1 increased cell numbers and delayed differentiation, as evidenced by reduced expression of differentiation markers. The study concluded that androgens upregulated Odc1 via the AR, promoting myoblast proliferation and delaying differentiation.

The study investigated the expression patterns of ornithine decarboxylase (ODC) and keratins in early papillomas in SENCAR mice to identify markers for early skin tumorigenesis. Tumors were induced using 7,12-dimethylbenzanthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate. In early papillomas, keratin K1 showed patchy staining, while K10 was minimally expressed, contrasting with their normal expression in mildly hyperplastic epidermis. ODC expression was intense and diffuse in suprabasal cells of papillomas, correlating with decreased K1 and K10 expression, indicating altered differentiation. These findings suggested that high ODC expression and reduced K1 and K10 could serve as markers for early tumorigenesis in mouse skin.

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 demonstrated that elevated levels of ornithine decarboxylase (ODC) and polyamines, when combined with a mutant Ha-ras gene, led to spontaneous tumor development in double transgenic mice. These mice, which were bred to carry both K6/ODC and v-Ha-ras transgenes, developed well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The tumor development was dependent on ODC, as the use of the ODC inhibitor DFMO prevented tumor formation and caused regression. This indicated that ODC overexpression and activated Ha-ras were sufficient for malignant transformation, providing a model to study epithelial tumor development without chemical carcinogens or tumor promoters.

The study investigated the expression of ornithine decarboxylase (ODC) in mouse skin treated with the tumor promoter TPA. It was found that ODC expression was heterogeneous, with high levels predominantly in suprabasal cells around hair follicles shortly after TPA treatment. This expression was transient, disappearing within 16 to 24 hours, but persisted in some cells within benign papillomas a week after TPA application. Pretreatment with retinoic acid or cycloheximide inhibited ODC expression. The findings suggested that both normal and tumor tissues in mice exhibited varied ODC expression.

The study investigated the effects of multiple exposures to 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein, and ethyl phenylpropriolate (EPP) on murine epidermal cells, focusing on the induction of ornithine decarboxylase (ODC) activity. While single applications of these agents caused similar hyperplasia and ODC induction, multiple treatments revealed significant differences in ODC activity, with TPA and mezerein inducing more than EPP. Immunocytochemical analysis showed distinct patterns of ODC-positive cells, with TPA prominently affecting perifollicular cells, mezerein affecting both interfollicular and perifollicular areas, and EPP affecting only interfollicular cells. Flow cytometry identified three keratinocyte subpopulations, with TPA causing the expansion of an intermediate-sized subpopulation not seen with EPP or mezerein. The findings suggested that TPA, a potent tumor promoter, selectively expanded a keratinocyte subpopulation hyperinducible for ODC, potentially important for neoplastic transformation, while mezerein and EPP were less effective in this regard.

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.

The study used hairless Sprague Dawley rats to assess the ability of retinoids to inhibit epidermal ornithine decarboxylase activity induced by sellotape stripping. A total of 100 rats (50 males and 50 females) aged 4 to 11 weeks were examined to validate the model. The study found that hair growth occurred at 6-7 weeks and 10-11 weeks, with more pronounced growth in males. No histological changes were observed in the stratum corneum, but an increase in epidermal thickness was noted in 9-week-old males. Sellotape stripping was more effective and consistent in females, with lower individual variation (5%-10% in females vs. 10%-20% in males). The research concluded that female rats aged about 8 weeks provided the most reproducible response and ease of use for this model.

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.

Hair plucking in rats led to a rapid decrease in ornithine decarboxylase (ODC) activity, while other skin enzymes remained unaffected. The study suggested the presence of an inhibitor, known as antizyme, which was released early during the induction of ODC by hair plucking. Treatment with 10% (NH4)2SO4 increased ODC activity by approximately 75% in enzyme preparations, indicating that antizyme levels increased in plucked skin extracts after such treatment.

A transgenic mouse model was developed to overexpress ornithine decarboxylase (ODC) specifically in hair follicle keratinocytes using a regulated system. In the absence of doxycycline, these mice showed high levels of epidermal ODC activity and hyperplasia when exposed to the tumor promoter TPA, particularly affecting hair follicles. This effect was reversed by adding doxycycline, which repressed transgene expression. The study found that increased ODC expression made the typically tumor promotion-resistant C57Bl/6 mice more sensitive to TPA's effects, as evidenced by a reduction in papilloma development when ODC expression was repressed.

The study developed a transgenic mouse model to investigate the role of ornithine decarboxylase (ODC) in tumor promotion. By using a tetracycline-regulated system, researchers were able to overexpress ODC specifically in hair follicle keratinocytes of C57Bl/6 mice. In the absence of doxycycline, these mice showed high levels of epidermal ODC activity and hyperplasia when exposed to the tumor promoter TPA, particularly affecting hair follicles. This increased ODC expression made the typically tumor-resistant C57Bl/6 mice more sensitive to tumor-promoting effects. However, when doxycycline was used to repress ODC expression, the number of papillomas was significantly reduced, demonstrating the critical role of ODC 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.

The study presented a tracheal xenotransplantation assay as a simple in vivo system to evaluate epithelialization, hair follicle formation, and tumorigenesis using primary epidermal cells from wild-type and transgenic mice. This method involved seeding epithelial cells into deepithelialized rat tracheas, which were then transplanted into athymic nude mice. The study found that keratinocytes overexpressing ornithine decarboxylase (ODC) and infected with v-Ha-ras became invasive, penetrating all layers of the tracheal wall, similar to malignant skin carcinomas in ODC/Ras transgenic mice. The assay also demonstrated its utility in hair follicle reconstitution, showing that freshly harvested epithelial cells were more effective than cultured ones in forming hair follicles. The method proved advantageous for studying keratinocyte stem cell colonies and factors affecting hair follicle development, especially when cell numbers were limited.