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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.

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.

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 effects of TPA-stimulated polyamine biosynthesis on metastatic squamous cell carcinoma (mSCC) development in protein kinase C epsilon (PKC epsilon) transgenic mice. It was found that TPA treatment significantly increased epidermal ornithine decarboxylase (ODC) activity and putrescine levels in these mice compared to wild-type littermates. The development of mSCC was completely prevented by administering alpha-difluoromethylornithine (DFMO), an ODC inhibitor, in the drinking water during TPA promotion. However, this treatment resulted in marked hair loss and a decrease in intact hair follicles in the transgenic mice. The findings suggested a link between TPA-induced ODC activity, putrescine accumulation, hair follicle maintenance, and mSCC development, with the observed hair loss being a novel side effect not previously reported in other cancer prevention models.

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 used transgenic mice to investigate the role of MEK and Antizyme (AZ) in skin tumorigenesis and keratinocyte differentiation. Mice overexpressing MEK showed increased epidermal stem cell expansion and decreased keratinocyte differentiation, leading to epidermal hyperplasia and tumor development. However, co-expression of AZ reduced tumor development by decreasing ornithine decarboxylase (ODC) activity, which is linked to polyamine biosynthesis and tumor promotion. AZ expression counteracted MEK-induced effects, normalizing the number of transient amplifying (TA) cells and stem cells, and restoring differentiation marker levels in keratinocytes. The findings suggested that ODC and polyamines were crucial in regulating epidermal stem cell behavior and keratinocyte differentiation.

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.

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.