Keratinocyte stem cells: targets for cutaneous carcinogens

Morris, Rebecca J.

doi:10.1172/jci10508

Cited by 94 publications

(86 citation statements)

References 18 publications

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“…Epidermal stem cells that reside in a specific area of hair follicles were hypothesized to be target cells for skin carcinogenesis (Morris, 2000). We revealed that there was 25% reduction in the number of hair follicles in dorsal skin of K5-GR/ras+ transgenics (data not shown).…”

Section: Discussionmentioning

confidence: 86%

Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis

et al. 2003

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y These authors contributed equally to the work Glucocorticoids are effective inhibitors of epidermal proliferation and skin tumorigenesis. Glucocorticoids affect cellular functions via glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated skin-targeted transgenic mice overexpressing GR under control of the keratin5 promoter (K5-GR mice). To test the hypothesis that GR plays a role as a tumor suppressor in skin, we bred K5-GR transgenic mice with Tg.AC transgenic mice, which express v-Ha-ras oncogene in the skin, and compared the susceptibility of F1 offspring to TPA-induced skin carcinogenesis. GR overexpression in the epidermis dramatically inhibited skin tumor development. In K5-GR/ras+ double transgenic mice papillomas developed later and the average number of tumors per animal was 15% (in males) and 40% (in females) of the number seen in wild type (w.t./ras+) littermates. In addition, the papillomas in w.t./ras+ animals were eight to nine times larger. GR overexpression resulted in a decrease in keratinocyte proliferation combined with a modest increase in apoptosis and differentiation of keratinocytes in K5-GR/ras+ papillomas. Our data clearly indicate that interference of GR transgenic protein with nuclear factor kappa B (NF-jB) transcription factor had resulted in NF-jB blockage in K5-GR/ras+ tumors. We discuss the role of NF-jB blockage in tumor-suppressor effect of GR.

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Section: Discussionmentioning

confidence: 86%

Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis

et al. 2003

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“…TPA administration stimulates papilloma formation even when started a year after DMBA treatment, suggesting that the initial mutation arises in long-lived SCs (Morris et al 1986(Morris et al , 1997Morris 2000). The demonstration that tumors can form, although at lower frequency, when the IFE is removed by dermabrasion after DMBA and repaired by HF cells suggests that cancer-initiating cells may reside in the IFE as well as in HFs (Argyris and Slaga 1981).…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

Development and Homeostasis of the Skin Epidermis

Sotiropoulou

Blanpain

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe skin epidermis is a stratified epithelium that forms a barrier that protects animals from dehydration, mechanical stress, and infections. The epidermis encompasses different appendages, such as the hair follicle (HF), the sebaceous gland (SG), the sweat gland, and the touch dome, that are essential for thermoregulation, sensing the environment, and influencing social behavior. The epidermis undergoes a constant turnover and distinct stem cells (SCs) are responsible for the homeostasis of the different epidermal compartments. Deregulation of the signaling pathways controlling the balance between renewal and differentiation often leads to cancer formation.

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“…In order for latent neoplastic cells to persist in the skin, they must be slowly cycling to avoid removal to the suprabasal layers and loss by terminal differentiation, and they must reside within a protected niche or microenvironment within the skin (Lavker and Sun, 2000). Therefore, carcinogen target cells possess some qualities of a stem cell population (Morris, 2000). The most likely repository of keratinocyte stem cells (KSC) in the skin is the bulge region, which is located in the permanent portion of the hair follicle below the sebaceous gland at the point of attachment of the arrector pili muscle.…”

Section: Cellular Aspectsmentioning

confidence: 99%

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

et al. 2005

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Keratinocyte stem cells: targets for cutaneous carcinogens

Abstract: Figure 1Cross section of the epidermis demonstrating the epidermis (e) overlaying the dermis (d), and a hair follicle (hf) together with its sebaceous gland (sg). Original magnification, ×400.

Cited by 94 publications

References 18 publications

Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis

Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis

Development and Homeostasis of the Skin Epidermis

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

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