Disease relevance of SPRR3

• Initial screening by Southern blot analysis showed amplification of S100A6, FLG and SPRR3 in several sarcomas and, in a first attempt to characterize the 1q21-q22 amplicon in more detail, we have now investigated the amplification status of these and 11 other markers in the region in 35 sarcoma samples [1].
• By contrast, differentiating epidermal tumours such as Bowen's disease, keratoacanthoma and squamous cell carcinoma expressed SPRR3 [2].
• RESULTS: Increased suprabasal expression of SPRR1 and SPRR2, but no SPRR3 expression, was noted in inflammatory dermatoses with orthokeratotic and parakeratotic squamous differentiation [2].
• Northern blot analysis revealed that cornifin-alpha mRNA was present in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was expressed in oral mucosal epithelia and verrucous carcinoma of the skin but neither in normal nor in psoriatic skin [3].
• PCR analysis of genes selected based on DNA array experiments revealed that estimation of the ratios of GATA6 to SPRR3 allows discrimination among normal esophageal epithelium, Barrett's dysplasia, and adenocarcinoma [4].

High impact information on SPRR3

• Whereas group 1 genes have diverged in protein structure and are composed of three different classes (SPRR1 (2x), SPRR3, and SPRR4), an active process of gene conversion has counteracted diversification of the protein sequences of group 2 genes (SPRR2 class, seven genes) [5].
• Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression [6].
• In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions [6].
• In the squamous dysplasias, there was more intense staining (of esophagin) in the atypical nuclei and superficial squamous epithelial cells than in the basal cells [6].
• Northern blot, dot blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that SPRR3 expression was lost in three cell lines of oesophageal carcinoma and was dramatically decreased in 54 out of 57 primary oesophageal carcinomas compared with adjacent normal mucosa [7].

Biological context of SPRR3

• Thus, SPRR1, SPRR2, and SPRR3 are differentially expressed in vivo and in vitro, suggesting that the SPRR multigene family evolved to serve as highly specialized cornified cell envelope precursor proteins in stratified epithelia [8].
• The repositioning of the SPRR3 Ets binding site during evolution has a major effect on the relative contribution of this site to promoter activity [9].
• In conjunction with published human in vivo studies, these data support the hypothesis that esophagin is a biomarker of esophageal squamous cell differentiation and provide an in vitro model to evaluate regulatory factors involved in this differentiation process [10].
• A genomic clone containing esophagin was isolated and sequenced, including 2.7 kb of the esophagin promoter region [10].

Anatomical context of SPRR3

• In the upper digestive tract, SPRR1 was expressed in sublingual and tongue epithelium, SPRR2 was mostly restricted to lingual papillae, and SPRR3 was abundant in oral and esophageal epithelium [8].
• Furthermore, detectable SPRR2 and SPRR3 levels were strongly increased in differentiating keratinocyte cultures after addition of LTB-2, a specific inhibitor of transglutaminases, suggesting that they are precursor proteins of the cornified cell envelope [8].
• Esophagin expression was studied in response to various treatments of primary cultured human esophageal epithelial cells and squamous cell carcinoma cell lines [10].

Associations of SPRR3 with chemical compounds

• Addition of 10(-7) M retinoic acid to cultured differentiating keratinocytes significantly down-regulated the expression of SPRR2 and SPRR3 transcripts and slightly decreased that of SPRR1 [8].

Regulatory relationships of SPRR3

• Loricrin and SPRR2 are expressed in the stratum granulosum and SPRR3 is absent [11].

Other interactions of SPRR3

• Loricrin is absent, and SPRR2 and SPRR3 expression extend into the spinous layers [11].
• The immunostaining patterns of esophagin and PCNA were evaluated and graded for level of expression [6].
• The deduced protein sequences of SPRC and SPRK were described and compared, and the relative abundance of their respective cDNAs in palatal and keratocyst libraries determined [12].
• Esophagin is a member of the small proline-rich protein family of cell envelope precursor proteins, which are expressed during squamous cell differentiation [10].

References