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SEL1L, an UPR response protein, a potential marker of colonic cell transformation.

Abstract：

BACKGROUND:SEL1L gene product is implicated in the endoplasmic reticulum (ER)-associated protein degradation and Unfolded Protein Response pathways. This gene and associated miRNAs have been indicated as predictive and prognostic markers of pancreatic cancer. AIM:Explore the role of SEL1L in colorectal cancer (CRC) progression. METHODS:SEL1L expression was analysed immunohistochemically in 153 adenomas and 71 CRCs from African American and North Italian patients. The distribution of stained cells was determined by computing median and inter quartile range. The receiver operating characteristics plot was used as discriminate power of SEL1L expression, CRC diagnosis and the effects on patient survival. RESULTS:SEL1L was low in normal mucosa and confined to few scattered cells at the base crypt of the villi and in the foveolar glandular compartment. The highest levels were in Paneth cells within the lysosomes. The enterocytic progenitor cells and mature enterocytes showed less cytoplasmic staining. In CRCs, SEL1L expression significantly correlated with the progression from adenoma to carcinoma (P = 0.0001) being stronger in well-to-moderately differentiated cancers. No correlation was found with other clinicopathological characteristics or ethnicity. CONCLUSIONS:SEL1L expression is a potential CRC tissue biomarker since its expression is significantly higher in adenoma cells with respect to normal mucosa. The levels of expression decrease sensibly in undifferentiated CRC cancers. Interestingly, Paneth cells contain high levels of SEL1L protein that could indicate pre-neoplastic mucosa undergoing neoplastic transformation. Since SEL1L's major function lies within ER stress and active ERAD response, it may identify CRCs with differentiated secretory phenotype and acute cellular stress.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Ashktorab H,Green W,Finzi G,Sessa F,Nouraie M,Lee EL,Morgano A,Moschetta A,Cattaneo M,Mariani-Costantini R,Brim H,Biunno I

doi

10.1007/s10620-011-2026-y

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

905-12

issue

eissn

0163-2116

issn

1573-2568

journal_volume

pub_type

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SEL1L, an UPR response protein, a potential marker of colonic cell transformation.