The Malignant Capacity of Skin Tumors Induced by Expression of a Mutant H-Ras Transgene Depends on the Cell Type Targeted

April 1998 in “ Current Biology ”

Ken Brown, Douglas Strathdee, Sheila Bryson, Wendy Lambie, Allan Balmain

The study investigated the carcinogenic effects of expressing a mutant H-ras oncogene in different epidermal cell populations of mice. It found that targeting the expression to follicular and interfollicular cells using a truncated keratin 5 gene promoter led to the development of acanthotic areas and carcinoma in situ in newborn mice, and papillomas and keratoacanthomas in adults. These benign tumors frequently progressed to malignancy, unlike those induced by other promoters, and did not require wounding or a tumor promoter for formation. The research concluded that the cell type in which tumor initiation occurs, particularly within the hair follicle, significantly influenced the malignant potential of the tumors.

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research Ornithine Decarboxylase Overexpression Is a Sufficient Condition for Tumor Promotion in Mouse Skin

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.

research Skin-Specific Expression of a Truncated E1a Oncoprotein Binding to p105-Rb Leads to Abnormal Hair Follicle Maturation Without Increased Epidermal Proliferation

30 citations, June 1993 in “The Journal of Cell Biology”

In this study, researchers investigated the effects of a mutant Adenovirus E1a oncoprotein, NTdl646, on keratinocyte growth and differentiation in transgenic mice. The protein was expressed specifically in the skin using a keratin 5 promoter, resulting in two lines of mice with abnormal hair phenotypes, including short, crooked hair shafts and dystrophic or absent inner root sheaths. Despite these hair follicle maturation disturbances, the interfollicular epidermis remained normal, and there was no increase in spontaneous or chemically induced skin tumors. The study concluded that while the transgene disrupted keratinocyte maturation, it did not lead to increased epidermal proliferation or neoplastic growth.

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research Hair Follicle-Specific Keratins And Their Diseases

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Only a few hair-specific keratins are linked to inherited hair disorders.

research Hair Keratin Pattern in Human Hair Follicles Grown In Vitro

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