The effects of
selenium, an essential nutrient with anti-carcinogenic properties, are mediated by
selenium-binding proteins. The
protein expression status of human
selenium-binding protein 1 (SBP1) in human tumours and the exact function of this
protein are not known. In this study, quantitative two-dimensional
polyacrylamide gel electrophoresis (2-D PAGE) was used on 93
lung adenocarcinomas and ten uninvolved lung samples. Two likely
isoforms of a 56 kD
protein that showed a significantly decreased abundance in
lung adenocarcinomas were observed. Tandem mass spectrometry and 2-D western blot analysis identified these two
proteins as human SBP1. Tumour tissue microarrays were utilized to examine the cellular expression patterns of SBP1 using immunohistochemistry. The same tissue samples were examined for SBP1
mRNA expression using
oligonucleotide microarrays. Two major SBP1
isoforms were detected, with an acidic
isoform (457) being significantly down-regulated in
lung adenocarcinomas compared with normal lung (p = 0.02). Two additional more acidic SBP1
isoforms were only observed in normal lung. SBP1
protein isoforms and SBP1
mRNA levels were significantly decreased in poorly differentiated (versus moderately and well-differentiated), T2-T4 (versus T1), and bronchus-derived (versus bronchioloalveolar) tumours. Low levels of SBP1
protein (native form, 460) correlated significantly with poor survival (p = 0.007). The lack of SBP1 expression was not due to gene deletion. Treatment of A549
lung adenocarcinoma cells with the methylation inhibitor
5-azacytidine did not affect expression of the SBP1
protein. Analysis of the tumour proliferation status using Ki-67 suggests that down-regulated expression of SBP1 may reflect increased cell proliferation and decreased differentiation in
lung adenocarcinomas.