TL;DR: A human stomach‐specific protein, 18 kDa antrum mucosa protein, was found to be dramatically under‐expressed in cancer tissues, implicating a possible special pathological role for this protein in gastric carcinogenesis.
Abstract: Gastric adenocarcinoma is one of the most common cancers in Asian countries including China. Although its incidence rates in the West are lower than that in Asia, gastric cancer is still a major health problem worldwide, being second only to lung cancers in the number of deaths it causes. Helicobacter pylori infection has been identified as the major pathogen, but the detailed pathogenesis of gastric carcinoma remains elusive. Due to the lack of suitable and specific biomarkers for early detection, most cases of the disease are diagnosed at late stages and the survival rate is low. In this study, we used a proteomic approach to globally analyze the protein profiles of paired surgical specimens of primary gastric adenocarcinoma and nontumor mucosa aiming at identifying specific disease-associated proteins as potential clinical biomarkers and for carcinogenetic study. Compared to nontumor tissues, multiple protein alterations were found in tumor tissues. Some of these alterations involve variations in the expression of cytoskeleton proteins, including an increase in cytokeratin 8 and tropomyosin isoform and a decrease in cytokeratin 20. Co-up-regulations of heat-shock proteins and glycolytic enzymes were observed in tumor tissues, indicating self-protective efforts of cells and the growing energy requirement during malignant transformation. Diverse regulations also occurred with proteins involved in cell proliferation and differentiation, such as GMP reductase 2 and creatine kinase B, and proteins bearing potential tumor suppressor activities, including prohibitin and selenium binding protein 1. More interestingly, a human stomach-specific protein, 18 kDa antrum mucosa protein, was found to be dramatically under-expressed in cancer tissues, implicating a possible special pathological role for this protein in gastric carcinogenesis. Further comprehensive evaluation by globally considering the altered factors may result in the discovery of a biomarker index for effective assessment of the disease and may provide in-depth information for better understanding the pathogenesis of gastric cancer.
TL;DR: This is the first report of a specific protein to which a metabolite of acetaminophen covalently binds, and the amino acid sequence from a cDNA corresponds to a 56 kDa selenium binding protein.
TL;DR: HSP56 expression was especially high in normal tissues that appear to benefit from the cancer-protective action of dietary selenium and was low in many neoplastic cells, suggesting that hSP56 may play a role in determining the neoplastics phenotype.
Abstract: Low levels of dietary selenium are associated with increased risk of malignancy of several organs, including the prostate. Using a subtractive approach called linker capture subtraction, we have found that the human selenium-binding protein gene hSP56 is differentially expressed by the relatively slow-growing, androgen-sensitive prostate cancer cell line LNCaP but not by the more rapidly growing androgen-insensitive lines PC-3 and DU145. We confirmed this differential expression by Northern blot analysis. Importantly, hSP56 expression by LNCaP cells was reversibly down-regulated by exogenous androgen in a concentration-dependent manner. Marked differences in steady-state hSP56 mRNA levels were found in a variety of normal and neoplastic human cells that were examined. hSP56 expression was especially high in normal tissues that appear to benefit from the cancer-protective action of dietary selenium and was low in many neoplastic cells. The results suggest that hSP56 may play a role in determining the neoplastic phenotype.
TL;DR: Data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
Abstract: To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
TL;DR: Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes, and uses reverse transcription/PCR with oligonucleotide primers to distinguish the AP56 and SP56 mRNAs to evaluate the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.
Abstract: A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.