High Levels of c-fos Proto-Oncogene Expression in Normal Human Adult Skin

Basset-Séguin, Nicole; Escot, Chantal; Blanchard, Jean Marie; Kerai, Cécile.; Verrier, Bernard; Mion, H; Guilhou, Jean Jacques

doi:10.1111/1523-1747.ep12874493

Cited by 38 publications

(17 citation statements)

References 28 publications

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“…Examples are the exercise of skeletal muscle (Osbaldeston et al, 1995), ballooning and other forms of mechanical injury to the arterial wall (Bauters et al, 1992), contraction by fibroblasts of collagen gels (Rosenfeldt et al, 1998), and stretch or pressure overload of cardiac muscle (Schunkert et al, 1991) and constitutively in skin (Basset-Seguin et al, 1990). Fos expression is induced, moreover, under various conditions in which PMD has not been investigated but might occur.…”

Section: Discussionmentioning

confidence: 99%

Temporary Disruption of the Plasma Membrane Is Required for c-fos Expression in Response to Mechanical Stress

Grembowicz

Sprague

McNeil

1999

MBoC

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Mechanically stressed cells display increased levels of fos message and protein. Although the intracellular signaling pathways responsible for FOS induction have been extensively characterized, we still do not understand the nature of the primary cell mechanotransduction event responsible for converting an externally acting mechanical stressor into an intracellular signal cascade. We now report that plasma membrane disruption (PMD) is quantitatively correlated on a cell-by-cell basis with fos protein levels expressed in mechanically injured monolayers. When the population of PMD-affected cells in injured monolayers was selectively prevented from responding to the injury, the fos response was completely ablated, demonstrating that PMD is a requisite event. This PMD-dependent expression of fos protein did not require cell exposure to cues inherent in release from cell-cell contact inhibition or presented by denuded substratum, because it also occurred in subconfluent monolayers. Fos expression also could not be explained by factors released through PMD, because cell injury conditioned medium failed to elicit fos expression. Translocation of the transcription factor NF-B into the nucleus may also be regulated by PMD, based on a quantitative correlation similar to that found with fos. We propose that PMD, by allowing a flux of normally impermeant molecules across the plasma membrane, mediates a previously unrecognized form of cell mechanotransduction. PMD may thereby lead to cell growth or hypertrophy responses such as those that are present normally in mechanically stressed skeletal muscle and pathologically in the cardiovascular system.

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Section: Discussionmentioning

confidence: 99%

Temporary Disruption of the Plasma Membrane Is Required for c-fos Expression in Response to Mechanical Stress

Grembowicz

Sprague

McNeil

1999

MBoC

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“…They observed that UVB induced an immediate early response of c-fos that was down-regulated within 2 h and a strong second phase of c-fos induction, which peaked at 8 h and returned to basal level after 24 h. They suggested that UVB-irradiated cells may release a factor with the ability to induce the second phase of c-fos induction. In addition, continuous expression of the c-fos gene has been reported in normal human skin under physiological conditions (33,39).…”

Section: Fig 5 Analyses Of Ap-1 Family Proteins After Uvb Irradiatimentioning

confidence: 99%

UVB Irradiation-induced Activator Protein-1 Activation Correlates with Increased c-fos Gene Expression in a Human Keratinocyte Cell Line

Chen

Borchers

Dong

et al. 1998

Journal of Biological Chemistry

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“…The expression of keratinocyte transglutaminase as well as structural proteins such as involucrin, loricrin, profilaggrin, and SPRR also becomes evident at later stages of keratinocyte differentiation (1,2). Detailed analysis of the regulatory regions of these genes have demonstrated the importance of a number of transcription factors (TFs), such as AP1 and AP2 (13)(14)(15)(16). However, these TFs are also expressed in other organ systems and are not likely to ultimately determine which genes are uniquely expressed in keratinocytes.…”

mentioning

confidence: 99%

Characterization of the Regulatory Domains of the Human Skn-1a/Epoc-1/Oct-11 POU Transcription Factor

Hildesheim¹,

Foster²,

Chamberlin³

et al. 1999

Journal of Biological Chemistry

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The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis. Although some POU factors expressed in a tissue-specific manner are important for normal differentiation, the biological function of Skn-1a remains unknown. Previous in vitro studies indicate that Skn-1a has the ability to transactivate markers of keratinocyte differentiation. In this study, we have characterized Skn-1a's transactivation domain(s) and engineered a dominant negative protein that lacked this transactivation domain. Deletional analysis of the human homologue of Skn-1a with three target promoters revealed the presence of two functional domains: a primary Cterminal transactivation domain and a combined N-terminal inhibitory domain and transactivation domain. Skn-1a lacking the C-terminal region completely lost transactivation ability, irrespective of the promoter tested, and was able to block transactivation by normal Skn-1a in competition assays. Compared with fulllength, Skn-1a lacking the N-terminal region demonstrated either increased transactivation (bovine cytokeratin 6 promoter), comparable transactivation (human papillomavirus type 1a long control region), or loss of transactivation (human papillomavirus type 18 long control region). The identification of a primary C-terminal transactivation domain enabled us to generate a dominant negative Skn-1a factor, which will be useful in the quest for a better understanding of this keratinocyte-specific gene regulator.

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High Levels of c-fos Proto-Oncogene Expression in Normal Human Adult Skin

Cited by 38 publications

References 28 publications

Temporary Disruption of the Plasma Membrane Is Required for c-fos Expression in Response to Mechanical Stress

Temporary Disruption of the Plasma Membrane Is Required for c-fos Expression in Response to Mechanical Stress

UVB Irradiation-induced Activator Protein-1 Activation Correlates with Increased c-fos Gene Expression in a Human Keratinocyte Cell Line

Characterization of the Regulatory Domains of the Human Skn-1a/Epoc-1/Oct-11 POU Transcription Factor

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