LKB1 regulates epithelial-mesenchymal transition in Peutz-Jeghers hamartoma and intestinal epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells.</p><p><b>METHODS</b>Immunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays. Western blotting, quantitative real-time PCR (qPCR) and immunofluorescence were used to assess the alterations of EMT markers in the cells with LKB1 knockdown.</p><p><b>RESULTS</b>Compared with normal intestinal tissues, hamartoma polyps showed significantly decreased LKB1 and E-cadherin expressions and increased vimentin expression with increased collagen fiber deposition. The cells with LKB1 knockdown exhibited enhanced cell proliferation and migration activities (P<0.01). Western blot analysis, qPCR and immunofluorescence all detected decreased E-cadherin and increased N-cadherin, vimentin, Snail, and Slug expressions in the cells with LKB1 knockdown.</p><p><b>CONCLUSION</b>s LKB1 deficiency triggers EMT in intestinal epithelial cells and Peutz-Jeghers hamartoma, suggesting that EMT can serve as the therapeutic target for treatment of Peutz-Jeghers syndrome.</p>

Expression of the proteins associated with transforming growth factor-beta/Smad signaling pathway in Peutz-Jeghers syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of important proteins associated with transforming growth factor-beta (TGF-beta)/Smad signaling pathway in Peutz-Jeghers syndrome (PJS) and investigate the correlation of these proteins to LKB1 gene expression.</p><p><b>METHODS</b>The expression and localization of LKB1, TGFbeta1 and pSmad2 proteins in 20 PJS polyp samples and normal intestinal mucosal tissues were detected with immunohistochemical staining.</p><p><b>RESULTS</b>The expressions of LKB1, TGFbeta1 and pSmad2 were lower in PJS polyps than in normal mucosa, and the differences in LKB1 and TGFbeta1 proteins were significantly different between them (P<0.05). In PJS polyps, positive correlations were found between LKB1 and TGFbeta1 and between TGFbeta1 and pSmad2 expressions.</p><p><b>CONCLUSION</b>TGFbeta/Smad pathway is probably subjected to the regulation by LKB1 and may play a role in the occurrence of PJS.</p>

Expression and significance of interferon-inducible transmembrane protein-1 gene in Peutz-Jeghers syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the mRNA and protein expression of interferon-inducible transmembrane protein-1 (IFITM1) in Peutz-Jeghers syndrome (PJS) and investigate the role of IFITM1 in the occurrence, development and carcinogenesis of PJS polyps.</p><p><b>METHODS</b>Reverse transcription-PCR was employed to detect the mRNA expression of IFITM1 in 16 PJS polyp samples, adenomatous polyp tissues, colon adenocarcinoma samples, and normal intestinal mucosal tissues. The protein expression and localization of IFITM1 in these tissues (32 cases for each) were detected with immunohistochemical (IHC) staining.</p><p><b>RESULTS</b>The IFITM1 mRNA expression was detected in all these tissues, and the expression intensity increased in the order of normal intestinal mucosa, PJS polyp, adenomatous polyp, and colon adenocarcinoma (F=92.704, P=0.000). IHC revealed that IFITM1 protein was localized mainly on the cell membrane and in the cytoplasm, with increased expression intensity in the same order as its mRNA and showing significant differences between the tissues by several rank-sum test (Kruskal-Wallis H, chi(2)=37.036, p=0.000).</p><p><b>CONCLUSION</b>The expression level of IFITM1 is associated with the progression of the carcinogenetic process in PJS polyp, and can be used as a sensitive biomarker for diagnosis and prognostic evaluation of PJS.</p>

Association of peripheral blood estradiol, progesterone and testosterone levels with irritable bowel syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relation of peripheral blood estradiol, progesterone and testosterone levels with irritable bowel syndrome (IBS).</p><p><b>METHODS</b>Forty-eight patients with IBS identified according to Rome II diagnostic criteria and 30 healthy subjects as controls were analyzed for peripheral blood sex hormone levels by radioimmunoassay and corresponding software.</p><p><b>RESULTS</b>In male patients with IBS, blood testosterone level was significantly lower than that of the control group (P<0.05), but blood estradiol and progesterone showed no significant differences between the two groups (P>0.05). In the female patients, blood estradiol level was significantly lower than that of the control group (P<0.05), whereas blood progesterone and testosterone levels had no significant differences between the two groups (P>0.05).</p><p><b>CONCLUSION</b>Peripheral blood testosterone level in male IBS patients and estradiol level in female patients are lower than those of healthy subjects, suggesting that IBS might be associated with blood sex hormone disorder.</p>

Contribution of eukaryotic initiation factor-4E inhibition to heparanase expression and activity in human colon adenocarcinoma cell line LS-174T / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine whether the eukaryotic initiation factor-4E (eIF-4E) is involved in the cap-dependent translational regulation of heparanase and study the correlation between heparanase expression and metastatic potential of LS-174T cells.</p><p><b>METHODS</b>The protein and mRNA levels of inhibited eIF-4E were tested by Western blot and RT-PCR. Heparanase activity was defined as the ability to degrade high molecular weight (40-100 000) radiolabeled ((35)S) heparan sulfate (HS) substrate into low molecular weight (5-15 000) HS fragments. The invasive potential of tumor cells in vitro was observed by Matrigel invasion assay system.</p><p><b>RESULTS</b>The 20-mer antisense oligonucleotide (asODN) against eIF-4E specifically and significantly inhibited eIF-4E expression at both transcriptional and translational levels. The expression and the activity of heparanase were effectively lowered, which further decreased the invasive potential of LS-174T.</p><p><b>CONCLUSION</b>eIF-4E, probably being involved in translational regulation of heparanase in colon adenocarcinoma cell line LS-174T, can be a particularly interesting target for heparanase regulation, based on of its critical function.</p>