Transient activation of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours

Celso, Cristina Lo; Prowse, David M.; Watt, Fiona M.

doi:10.1242/dev.01052

Cited by 318 publications

(343 citation statements)

References 69 publications

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“…Since mice undergo two sequential waves of hair growth before entering a prolonged telogen phase at 6 weeks of age (Muller-Rover et al, 2001;Stenn and Paus, 2001), we began the 4OHT treatment at 6 weeks of age to ensure that the follicles would be in telogen for at least 3 weeks after initiating the 4OHT treatment. No hair regrowth was observed in the skin of transgenic mice treated with ethanol alone or wild-type mice treated with 4OHT (data not shown), as previously reported (Van Mater et al, 2003;Lo Celso et al, 2004). In contrast, drastic changes were detected in the transgenic mice treated with 4OHT ( Figure 2).…”

Section: Induction Of Epidermal Hyperplasia By Akt Signaling Activatisupporting

confidence: 87%

“…The activation of Wnt/b-catenin signaling brings about similar phenotypes in adult epidermis (Gat et al, 1998;Van Mater et al, 2003;Lo Celso et al, 2004). The mice expressing stabilized b-catenin or b-cateninMer fusion protein show epidermal hyperplasia, hair follicle tumor-like outgrowth and precocious transition from telogen to anagen phase via activation of stem cells.…”

Section: Proliferation Of Keratinocyte Progenitors By Akt Signalingmentioning

confidence: 99%

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Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

Murayama¹,

Kimura²,

Tarutani

et al. 2007

Oncogene

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Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/b-catenin signals. Phosphoinositide-3 kinase (PI3K)/Akt signaling regulates the 'stemness' of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.

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Section: Induction Of Epidermal Hyperplasia By Akt Signaling Activatisupporting

confidence: 87%

Section: Proliferation Of Keratinocyte Progenitors By Akt Signalingmentioning

confidence: 99%

Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

Murayama¹,

Kimura²,

Tarutani

et al. 2007

Oncogene

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show abstract

“…47 This hypothesis is supported by the observation that overexpression of molecules associated with normal self-renewal induces tumor formation by stem cells derived from normal adult tissue. 48 The reactivation of pluripotency-associated genes has been also observed in various somatic cancer cells. 49 Finally, manipulation in normal stem cells of some self-renewal pathways, such as Oct4, can also lead to cancer.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

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“…These signals exist as a delicate "Yin & Yang" balance between positive and negative regulators. Using genetic models, key factors of the Wnt signaling pathway have been shown to be essential for promoting stem cell self-renewal in various systems [14][15][16][17][18][19][20]. Notch and hedgehog signaling pathways have also been demonstrated to play crucial regulatory roles for self-renewal regulation of HSCs [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Beyond tumorigenesis: cancer stem cells in metastasis

et al. 2006

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Transient activation of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours

Abstract: SummaryTransient activation of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours

Cited by 318 publications

References 69 publications

Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Beyond tumorigenesis: cancer stem cells in metastasis

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