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Expression of caspase 14 and filaggrin in oral squamous carcinoma.

ABSTRACT: Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematically evaluated for caspase 14 expression yet. Formalin-fixed and paraffin-embedded samples from oral squamous carcinomas (n = 36 tumours from 34 patients), metastases (n = 15) and controls (leukoplakia, n = 10) were analysed by immunohistochemistry. In carcinomas, human papilloma virus (HPV) infection was tested by PCR. Here we demonstrate that, in oral epithelia, caspase 14 is expressed mainly by cells of the intermediate and superficial cell layers while filaggrin is expressed only in keratinising foci in leukoplakia. Caspase 14 and filaggrin are co-localised. In invasive oral carcinomas, reduced expression of caspase 14 was detectable in 47 % of tumours but was not associated with keratinisation, tumour differentiation or HPV infection. Filaggrin was detectable in a subfraction of tumours (56 %) and was restricted to keratinising areas of the carcinomas. In summary, in contrast to cervical carcinomas, partial loss of caspase 14 is not associated with dedifferentiation in neoplastic lesions of the oral mucosa or HPV infection.

SUBMITTER: Scharenberg C

PROVIDER: S-EPMC3824792 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Expression of caspase 14 and filaggrin in oral squamous carcinoma.

Scharenberg Constance C Eckardt André A Tiede Christina C Kreipe Hans H Hussein Kais K

Head and neck pathology 20130504 4

Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematicall ...[more]

PMID: 23645350

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Project description:BackgroundLow epidermal filaggrin (FLG) is a risk factor for atopic dermatitis (AD) and allergic comorbidity. FLG mutations do not fully explain the variation in epidermal FLG levels, highlighting that other genetic loci may also regulate FLG expression.ObjectiveWe sought to identify genetic loci that regulate FLG expression and elucidate their functional and mechanistic consequences.MethodsA genome-wide association study of quantified skin FLG expression in lesional and baseline non(never)-lesional skin of children with AD in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort was conducted. Clustered regularly interspaced short palindromic repeat approaches were used to create isogenic human keratinocytes differing only at the identified variant rs11652075, and caspase recruitment domain family member 14 (CARD14)-deficient keratinocytes for subsequent mechanistic studies.ResultsThe genome-wide association study identified the CARD14 rs11652075 variant to be associated with FLG expression in non(never)-lesional skin of children with AD. Rs11652075 is a CARD14 expression quantitative trait locus in human skin and primary human keratinocytes. The T variant destroys a functional cytosine-phosphate-guanine site, resulting in reduced cytosine-phosphate-guanine methylation at this site (but not neighboring sites) in TT and CT compared with CC primary human keratinocytes and Mechanisms of Progression of Atopic Dermatitis to Asthma in Children children's skin samples, and rs11652075 increases CARD14 expression in an allele-specific fashion. Furthermore, studies in clustered regularly interspaced short palindromic repeat-generated CC and TT isogenic keratinocytes, as well as CARD14-haplosufficient and deficient keratinocytes, reveal that IL-17A regulates FLG expression via CARD14, and that the underlying mechanisms are dependent on the rs11652075 genotype.ConclusionsOur study identifies CARD14 as a novel regulator of FLG expression in the skin of children with AD. Furthermore, CARD14 regulates skin FLG homeostasis in an rs11652075-dependent fashion.

Dataset Information

Expression of caspase 14 and filaggrin in oral squamous carcinoma.

Publications

Expression of caspase 14 and filaggrin in oral squamous carcinoma.

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