Publications (6)22.75 Total impact
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Article: STK31 Maintains the Undifferentiated State of Colon Cancer Cells.
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ABSTRACT: The expression of serine/threonine kinase (STK) family is frequently altered in human cancers. However, the functions of these kinases in cancer development remain elusive. Here, we report that STK31 is robustly and heterogeneously expressed in colon cancer tissues and plays a critical role in determining the differentiation state of colon cancer cells. Knockdown or overexpression of STK31 induced or inhibited differentiation of colon cancer cells, respectively. Deletion of the STK domain abolished the inhibiting effect of STK31. Associated with differentiation, knockdown of STK31 resulted in significant suppression of tumorigenicity both in vitro and in vivo. Genome microarray analysis showed that knockdown of STK31 altered the expression profile of genes that are known to be involved in germ cell and cancer differentiation. Taken together, these results suggest that STK31 is able to control the differentiation state of colon cancer cells, which critically depends on its STK domain. The present findings may shed light on the new therapeutic approach against cancer by targeting STK31 and cancer differentiation.Carcinogenesis 07/2012; · 5.70 Impact Factor -
Article: Developmental expression and function of DKKL1/Dkkl1 in humans and mice.
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ABSTRACT: Experiments were designed to identify the developmental expression and function of the Dickkopf-Like1 (DKKL1/Dkkl1) gene in humans and mice. Mouse testes cDNA samples were collected at multiple postnatal times (days 4, 9, 18, 35, and 54, as well as at 6 months) and hybridized to Affymetrix mouse whole genome Genechips. To further characterize the homologous gene DKKL1 in human beings, the expression profiles between human adult testis and foetal testis were compared using Affymetrix human Genechips. The characteristics of DKKL1/Dkkl1 were analysed using various cellular and molecular biotechnologies. The expression of Dkkl1 was not detected in mouse testes on days 4 or 9, but was present on days 18, 35, and 54, as well as at 6 months, which was confirmed by RT-PCR and Western blot results. Examination of the tissue distribution of Dkkl1 demonstrated that while Dkkl1 mRNA was abundantly expressed in testes, little to no expression of Dkkl1 was observed in the epididymis or other tissues. In an in vitro fertilization assay, a Dkkl1 antibody was found to significantly reduce fertilization. Human Genechips results showed that the hybridization signal intensity of DKKL1 was 405.56-fold higher in adult testis than in foetal testis. RT-PCR analysis of multiple human tissues indicated that DKKL1 mRNA was exclusively expressed in the testis. Western blot analysis also demonstrated that DKKL1 was mainly expressed in human testis with a molecular weight of approximately 34 kDa. Additionally, immunohistochemical staining showed that the DKKL1 protein was predominantly located in spermatocytes and round spermatids in human testes. An examination of the expression levels of DKKL1 in infertile male patients revealed that while no DKKL1 appeared in the testes of patients with Sertoli cell only syndrome (SCOS) or cryptorchidism, DKKL1 was observed with variable expression in patients with spermatogenic arrest. These results, together with previous studies, suggest that DKKL1/Dkkl1 may play an important role in testicular development and spermatogenesis and may be an important factor in male infertility.Reproductive Biology and Endocrinology 07/2012; 10:51. · 2.05 Impact Factor -
Article: Whole-genome synthesis and characterization of viable S13-like bacteriophages.
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ABSTRACT: Unprecedented progresses in high-throughput DNA sequencing and de novo gene synthesis technologies have allowed us to create living organisms in the absence of natural template. The sequence of wild-type S13 phage genome was downloaded from GenBank. Two synonymous mutations were introduced into wt-S13 genome to generate m1-S13 genome. Another mutant, m2-S13 genome, was obtained by engineering two nonsynonymous mutations in the capsid protein coding region of wt-S13 genome. A chimeric phage genome was designed by replacing the F capsid protein open reading frame (ORF) from phage S13 with the F capsid protein ORF from phage G4. The whole genomes of all four phages were assembled from a series of chemically synthesized short overlapping oligonucleotides. The linear synthesized genomes were circularized and electroporated into E.coli C, the standard laboratory host of S13 phage. All four phages were recovered and plaques were visualized. The results of sequencing showed the accuracy of these synthetic genomes. The synthetic phages were capable of lysing their bacterial host and tolerating general environmental conditions. While no phenotypic differences among the variant strains were observed when grown in LB medium with CaCl(2), the S13/G4 chimera was found to be much more sensitive to the absence of calcium and to have a lower adsorption rate under calcium free condition. The bacteriophage S13 and its variants can be chemically synthesized. The major capsid gene of phage G4 is functional in the phage S13 life cycle. These results support an evolutional hypothesis which has been proposed that a homologous recombination event involving gene F of quite divergent ancestral lineages should be included in the history of the microvirid family.PLoS ONE 01/2012; 7(7):e41124. · 4.09 Impact Factor -
Article: A novel nonsense mutation in the androgen receptor gene causes the complete androgen insensitivity syndrome.
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ABSTRACT: We identified an unusual novel nonsense mutation in exon 3 of the androgen receptor (AR) gene in a patient with complete androgen insensitivity that was persistence of Wolffian derivatives. Sequence analysis revealed a substitution (C→T) at position 2211 and a deletion of G at position 2213 in exon 3 of the AR gene, resulting in the conversion of arginine(CGG) to a stop codon (TGA) of the AR. Western blotting demonstrated a truncated AR with around 70 kd was expressed. Histology of patient's testes showed that seminiferous tubules were totally filled with Sertoli cells without germ cells. Immunohistochemistry revealed positive AR localization in the nuclei of Sertoli cells and epithelia of efferent ductule and vas deferens. AR immunoexpression was stronger in the epithelia of efferent ductule and vas deferens than in Sertoli cells. The study extends the spectrum of exon 3 mutations in the AR gene.Journal of Andrology 07/2011; 33(3):357-60. · 2.97 Impact Factor -
Article: A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.
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ABSTRACT: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism.PLoS ONE 01/2010; 5(12):e15255. · 4.09 Impact Factor -
Article: Developmental expression pattern of a novel gene, TSG23/Tsg23, suggests a role in spermatogenesis.
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ABSTRACT: A novel gene, TSG23/Tsg23, was identified by comparing the expression profiles of human adult and fetal testis using Affymetrix Genechips. RT-PCR analysis from multiple human and mouse tissues indicated TSG23/Tsg23 mRNA was mainly expressed in the testis. In situ hybridization revealed that TSG23/Tsg23 mRNA was located in spermatocytes and round spermatids of the seminiferous tubules in human and mouse testis. To further confirm the result from RT-PCR, the antibody for human TSG23 was generated against the protein encoded by the gene. Western blot analysis demonstrated that TSG23 was mainly expressed in human testis, with a molecular weight of about 23 kDa. Immunohistochemistry showed that TSG23 was predominantly located in spermatocytes and round spermatids, consistent with the results from in situ hybridization. In order to explore the function of TSG23 in spermatogenesis, the study compared the expression of TSG23 in the testis from fertile persons and from patients with azoospermia. The results showed that there was less expression in patients with obstructive azoospermia compared with fertile persons, and no detectable TSG23 at mRNA and protein levels in patients with non-obstructive azoospermia. The expression of Tsg23 mRNA was considerably decreased in a time-dependent manner in the testis of an azoospermic mouse model induced by Busulfan. These data suggest that TSG23/Tsg23 is involved in human and mouse spermatogenesis.Molecular Human Reproduction 03/2009; 15(4):223-30. · 3.85 Impact Factor
