Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment.
Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [(33)P]dCTP and hybridized to GeneFilter GF211 microarray membranes (Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC (compared with control) and APF-treated (compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, alpha2-integrin, alpha1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, alpha2-integrin, and alpha-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.
Keay
Susan
S
Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. skeay@medicine.umaryland.edu
Seillier-Moiseiwitsch
Francoise
F
Zhang
Chen-Ou
CO
Chai
Toby C
TC
Zhang
Jialu
J
D000293:Adolescent; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000235:genetics* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D005796:Genes / Q000187:drug effects / Q000235:genetics; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D001743:Urinary Bladder / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*
D006131:Growth Inhibitors