title: Selenium-binding protein 1 is associated with the degree of colorectal cancer differentiation and is regulated by histone modification.
abstract: The aim of the present study was to examine the regulation of selenium binding protein 1 (SELENBP1) expression in colorectal cancer (CRC). Samples of cancer tissue and adjacent normal mucosa were collected from 83 CRC patients, and analyzed for SELENBP1 expression by 2D-DIGE, immunoblotting, RT-PCR and immunostaining. Expression levels of SELENBP1, carcinoembryonic antigen (CEA) and alkaline phosphatase (AKP) were determined in cultures of human colon cancer cell lines (SW480, SW620 and HT29) folllowing treatment with i) sodium butyrate (NaB, 2 mM), a differentiation inducer; ii) Trichostatin A (TSA, 0.3 µM), a histone deacetylase inhibitor; or iii) 5'-aza-2'-deoxycytidine (5-Aza-dC, 5 µM), a DNA methylation inhibitor. SELENBP1 expression was found to be downregulated (2.54-fold) in the CRC samples as determined by 2D-DIGE and confirmed by immunoblotting and RT-PCR. SELENBP1 expression was correlated with the degree of differentiation, but not with TNM stage or lymph node metastasis, and was higher in benign polyps (1.97±0.57) than in CRC tissues (0.96±0.59). In the CRC cell lines, NaB treatment led to the upregulation of SELENBP1, CEA and AKP when compared with the untreated cells (2.24- to 4.82-fold). SELENBP1 was also upregulated in cells treated with TSA alone (1.25- to 3.64-fold), or in combination with 5-Aza-dC (1.32- to 4.13-fold). In CRC, the downregulated SELENBP1 expression was reactivated by inducing differentiation. Therefore, SELENBP1 is a potential pharmacological target for individualized CRC treatment.
authors.affiliation: Department of General Surgery, The First Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Central Experimental Laboratory, The First Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The First Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yang
authors.affiliation: Central Experimental Laboratory, The First Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051137:Selenium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002272:Carcinoembryonic Antigen; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; D000469:Alkaline Phosphatase