{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:18:28Z","timestamp":1790504308320,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":6044,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1990,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cultured mouse keratinocytes can be initiated in vitro by the introduction of a v\u2010<jats:italic>ras<\/jats:italic><jats:sup>Ha<\/jats:sup> gene by viral transduction. Previous studies indicated that v\u2010<jats:italic>ras<\/jats:italic><jats:sup>Ha<\/jats:sup>\u2010transduced keratinocytes have a high proliferation rate in medium with 0.05 mM Ca<jats:sup>2+<\/jats:sup> and resist terminal differentiation in medium with &gt; 0.1 mM Ca<jats:sup>2+<\/jats:sup>, a culture condition in which normal cells mature into squames. The current studies demonstrate that v\u2010<jats:italic>ras<\/jats:italic><jats:sup>Ha<\/jats:sup> keratinocytes do not express transcripts or protein for epidermal early differentiation markers keratins 1 and 10 when cells are challenged with 0.12 mM Ca<jats:sup>2+<\/jats:sup>, which is a signal for expression of these genes in normal cells. Both transcript and protein for the late differentiation marker loricrin are also diminished in v\u2010<jats:italic>ras<\/jats:italic> keratinocytes, but filaggrin, also a late differentiation\u2010related gene product, is expressed in nearly normal amounts but at a different Ca<jats:sup>2+<\/jats:sup> optimum. Modification of intracellular Ca<jats:sup>2+<\/jats:sup> with ionomycin failed to restore the expression of any suprabasal keratinocyte markers. In contrast to the effects on normal products of keratinocyte differentiation, the introduction of the v\u2010<jats:italic>ras<\/jats:italic><jats:sup>Ha<\/jats:sup> gene facilitated the expression of keratins 8 (K8) and 18 (K18). These keratins are characteristic of embryonic cells and cells of simple adult epithelia but not stratified squamous epithelia such as skin. Like normal differentiation markers, the expression of K8 and K18 was dependent both on the v\u2010<jats:italic>ras<\/jats:italic> oncogene and the Ca<jats:sup>2+<\/jats:sup> concentration of the culture medium, with &gt; 0.1 mM Ca<jats:sup>2+<\/jats:sup> being optimal. At the optimal Ca<jats:sup>2+<\/jats:sup> level, the majority of v\u2010<jats:italic>ras<\/jats:italic> keratinocytes expressed K8 and K18 after 96 h, and many cells had reduced amounts of the normal keratinocyte cytokeratin K14. These studies indicate that the v\u2010<jats:italic>ras<\/jats:italic> gene causes substantial reprogramming of epidermal physiology, producing an unusual phenotype devoid of early suprabasal markers but at least partially permissive for late marker expression. Furthermore, the Ca<jats:sup>2+<\/jats:sup>\u2010dependent expression of K8 and K18 suggests that a normal signalling pathway used in keratinocyte differentiation is diverted to an abnormal endpoint.<\/jats:p>","DOI":"10.1002\/mc.2940030608","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T19:55:45Z","timestamp":1172087745000},"page":"363-373","source":"Crossref","is-referenced-by-count":50,"title":["The v\u2010<i>ras<\/i> oncogene inhibits the expression of differentiation markers and facilitates expression of cytokeratins 8 and 18 in mouse keratinocytes"],"prefix":"10.1002","volume":"3","author":[{"given":"Christina","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne 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