SEL1L, an UPR Response Protein, a Potential Marker of Colonic Cell Transformation
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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.
Explore the role of SEL1L in colorectal cancer (CRC) progression.
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.
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.
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.
KeywordsSEL1L expression Colorectal cancers Paneth’s cells
This work was supported in part by Grants #CA102681 and CA90890 funded by the National Cancer Institute, NIH, by the RCMI, by the Italian Government MIUR-FIRB grant nRBIP064CRT to IB, by Italian Government MIUR 60% grants to RMC for 2008 and 2009 and by a grant from “Associazione Italiana per la Ricerca sul Cancro” (AIRC) to AM. Dr. A. Morgano is a PhD student in the Oncology program at G. d’Annunzio University, Chieti, Italy.
Conflict of Interest
- 24.Liu Q, Chen J, Mai B, et al. A single-nucleotide polymorphism in tumor suppressor gene SEL1L as a predictive and prognostic marker for pancreatic ductal adenocarcinoma in caucasians. Mol Carcinog. 2011. (Epub ahead of print). doi: 10.1002/mc.20808.