Sequential expression of mRNA-encoded keratin sets in neonatal mouse epidermis: Basal cells with properties of terminally differentiating cells

Schweizer, Jürgen; Kinjo, Mitsuru; Fürstenberger, Gerhard; Winter, Hermelita

doi:10.1016/0092-8674(84)90311-8

Cited by 160 publications

(92 citation statements)

References 46 publications

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“…3 C-E), although some basal cells (Fig. 3D) were also labeled in all three founders, consistent with the previous demonstration that ≈10% of basal cells already express markers of suprabasal cells (39). InvCREER also labeled some cells of the companion layer of the HF, as well as suprabasal cells of the infundibulum (Fig.…”

Section: Resultssupporting

confidence: 75%

Identifying the cellular origin of squamous skin tumors

Lapouge

Youssef

Vokaer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

265

278

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Squamous cell carcinoma (SCC) is the second most frequent skin cancer. The cellular origin of SCC remains controversial. Here, we used mouse genetics to determine the epidermal cell lineages at the origin of SCC. Using mice conditionally expressing a constitutively active KRas mutant (G12D) and an inducible CRE recombinase in different epidermal lineages, we activated Ras signaling in different cellular compartments of the skin epidermis and determined from which epidermal compartments Ras activation induces squamous tumor formation. Expression of mutant KRas in hair follicle bulge stem cells (SCs) and their immediate progeny (hair germ and outer root sheath), but not in their transient amplifying matrix cells, led to benign squamous skin tumor (papilloma). Expression of KRas G12D in interfollicular epidermis also led to papilloma formation, demonstrating that squamous tumor initiation is not restricted to the hair follicle lineages. Whereas no malignant tumor was observed after KRas G12D expression alone, expression of KRas G12D combined with the loss of p53 induced invasive SCC. Our studies demonstrate that different epidermal lineages including bulge SC are competent to initiate papilloma formation and that multiple genetic hits in the context of oncogenic KRas are required for the development of invasive SCC.

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Section: Resultssupporting

confidence: 75%

Identifying the cellular origin of squamous skin tumors

Lapouge

Youssef

Vokaer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

265

278

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“…Spinous cells contain these four prekeratins in approximately equal quantities but by the time these cells reach the granular layer, the relative content of 'suprabasal' prekeratins is higher. Experiments on prekeratin synthesis in the different layers indicate that this is a consequence of altered gene expression (P. E. Bowden, unpublished data), in agreement with recent observations on cell-free translation of keratin mRNAs from mouse basal and spinous cells [41].…”

Section: Fig 4 Compavison Of Individual 125-i-labelledprekevutins (supporting

confidence: 76%

Proteolytic modification of acidic and basic keratins during terminal differentiation of mouse and human epidermis

Bowden

Quinlan

Breitkreutz

et al. 1984

European Journal of Biochemistry

112

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Keratins from the living cell layers of human and neonatal mouse epidermis (prekeratins) have been compared to those from the stratum corneum (SC keratins). Human and mouse epidermis contained four prekeratins, two ofeach keratin subfamily; type I1 basic (PI 6.5 -8.5 ; human 68 kDa, 60.5 kDa and mouse 67 kDa, 60 kDa) and type I acidic (PI 4.7 -5.7; human 57 kDa, 51 kDa and mouse 58 kDa, 53 kDa). While all four were present in equal amounts in adult human epidermis, two (67 kDa basic, 58 kDa acidic) were more prominent in neonatal mouse epidermis. Preliminary results with cell fractions (basal, spinous and granular) indicated that quantitative differences were a function of morphology, basal cells containing the smaller member of each subfamily and granular cells the larger. Mouse stratum corneum extracts contained four keratins (three in human): type 11 neutral -acidic (PI 5.7 -6.7; human 65 kDa and mouse 64 kDa, 62 kDa) and type I acidic (PI 4.9 -5.4; human 57.5 kDa, 55 kDa and mouse 58.5 kDa, 57.5 kDa). In both species, one-dimensional and two-dimensional peptide mapping (with V8 protease and trypsin respectively) indicated that while all four prekeratins were distinct gene products, similarities existed in the type I1 basic and the type I acidic keratin subfamilies. A strong homology also existed between type I1 SC keratins and the larger basic (type 11) prekeratin (human 68 kDa and mouse 67 kDa) and between type I SC keratins and the larger acidic (type I) prekeratin (human 57 kDa and mouse 58 kDa). These results indicate a precursor-product relationship within each keratin subfamily, between SC keratins and the prekeratins abundant in the adjacent granular layer. This differentiation-related keratin processing was similar in mouse and human epidermis, and may represent a widespread phenomenon amongst keratinising epithelia.

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“…Since involucrin (and hence Inv-MycER TAM ) is induced so early in the basal-suprabasal transition, it remains possible that it is even expressed at low level in basal keratinocytes (Schweizer et al, 1984;Watt, 1984;Regnier et al, 1986;Huitfeldt et al, 1991). Consequently, it is not possible to say whether involucrin-driven Myc acts to retain incipient suprabasal cells in cycle or instead to induce their re-entry.…”

Section: Discussionmentioning

confidence: 93%

Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia

et al. 2004

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The homeostatic integrity of skin epidermis is maintained by a balance between keratinocyte proliferation, on one hand, and terminal differentiation combined with outward migration and shedding, on the other. Perturbation of this balance in favor of proliferation can result in hyperplasia and, potentially, tumorigenesis. We have previously described a reversible transgenic mouse model of epidermal neoplasia in which expression of an acutely regulatable form of Myc, MycER TAM , is targeted to epidermis via the involucrin promoter. In this model, sustained activation of MycER TAM induces a complex neoplastic lesion involving marked hyperplasia of lessdifferentiated suprabasal cells, angiogenesis and overt papillomatosis. Subsequent deactivation of MycER TAM triggers complete papilloma regression. Here, we provide evidence that Myc-induced papillomas are self-limiting because of the eventual differentiation of MycER TAMexpressing keratinocytes. Thus, keratinocyte differentiation eventually prevails over Myc-induced proliferation. We also show that regression of Myc-induced papillomas following MycER TAM deactivation occurs through a combination of growth arrest and irreversible differentiation. Finally, we demonstrate that transient deactivation of Myc is sufficient to expel keratinocytes irreversibly from the proliferative compartment and render them refractory to the mitogenic influence of subsequent Myc reactivation. Such observations illustrate the potential utility of even short-term inhibition of oncogenic lesions in the treatment of cancer.

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Sequential expression of mRNA-encoded keratin sets in neonatal mouse epidermis: Basal cells with properties of terminally differentiating cells

Cited by 160 publications

References 46 publications

Identifying the cellular origin of squamous skin tumors

Identifying the cellular origin of squamous skin tumors

Proteolytic modification of acidic and basic keratins during terminal differentiation of mouse and human epidermis

Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia

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