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Squamous cell carcinomas and increased apoptosis in skin with inhibited Rel/nuclear factor-kappaB signaling
M van Hogerlinden1, B L Rozell, L Ahrlund-Richter
1Department of Bioscience at Novum, Karolinska Institute, NOVUM, Huddinge, Sweden.
Abstract:
The Rel/nuclear factor-kappaB (Rel/NF-kappaB) transcription factors have been implicated previously in control of apoptosis, cell proliferation, and oncogenesis. Here we show that selective inhibition of Rel/NF-kappaB signaling in murine skin, by targeted overexpression of a super-repressor form of IkappaB-alpha, results in an increased basal frequency of apoptotic cells and the spontaneous development of squamous cell carcinomas. Presence of hyperplasia and hair follicle degeneration demonstrate an important role for Rel/NF-kappaB signaling in normal epidermal development and homeostasis. Transgenic skin, in addition, showed an enhanced sensitivity to UV-induced apoptosis. These data suggest an involvement of the Rel/NF-kappaB signaling pathway in apoptosis and cancer development of the skin.
Insights
Inhibiting the Rel/nuclear factor-kappaB (NF-kB) pathway in mouse skin increases cell death and leads to spontaneous skin cancer. This pathway is crucial for normal skin development and repair.
Area of Science:
- Molecular Biology
- Oncology
- Dermatology
Background:
- The Rel/nuclear factor-kappaB (NF-kB) signaling pathway regulates key cellular processes including apoptosis, proliferation, and oncogenesis.
- Dysregulation of NF-kB is linked to various cancers, but its specific role in skin homeostasis and carcinogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of Rel/NF-kB signaling in murine skin development, homeostasis, and cancer formation.
- To determine the impact of selective Rel/NF-kB inhibition on UV-induced apoptosis and spontaneous tumor development.
Main Methods:
- Targeted overexpression of a super-repressor form of IkappaB-alpha in murine skin to selectively inhibit Rel/NF-kB signaling.
- Analysis of basal apoptosis frequency, epidermal development, hair follicle morphology, and spontaneous tumor incidence.
- Assessment of UV-induced apoptosis sensitivity in transgenic skin.
Main Results:
- Selective inhibition of Rel/NF-kB signaling resulted in increased basal apoptosis and spontaneous squamous cell carcinoma development.
- Evidence of hyperplasia and hair follicle degeneration indicated a critical role for Rel/NF-kB in epidermal homeostasis.
- Transgenic skin exhibited enhanced sensitivity to UV-induced apoptosis.
Conclusions:
- The Rel/NF-kB signaling pathway plays a significant role in regulating apoptosis and preventing spontaneous cancer development in the skin.
- Rel/NF-kB signaling is essential for normal epidermal development and maintaining skin homeostasis.
- Inhibition of this pathway increases skin susceptibility to UV-induced damage and cancer.