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APF mediates its antiproliferative activity in primary normal bladder epithelial cells via cytoskeletal associated protein 4 (CKAP4). Because synthetic asialo-APF (<jats:italic>as<\/jats:italic>-APF) has also been shown to inhibit T24 bladder cancer cell proliferation at nanomolar concentrations <jats:italic>in vitro<\/jats:italic>, and because the peptide segment of APF is 100% homologous to part of frizzled 8, we determined whether CKAP4 mediates <jats:italic>as<\/jats:italic>-APF inhibition of proliferation and\/or downstream Wnt\/frizzled signaling events in T24 cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>T24 cells were transfected with double-stranded siRNAs against CKAP4 and treated with synthetic <jats:italic>as<\/jats:italic>-APF or inactive control peptide; cells that did not undergo electroporation and cells transfected with non-target (scrambled) double-stranded siRNA served as negative controls. Cell proliferation was determined by <jats:sup>3<\/jats:sup>H-thymidine incorporation. Expression of Akt, glycogen synthase kinase 3\u03b2 (GSK3\u03b2), \u03b2-catenin, p53, and matrix metalloproteinase 2 (MMP2) mRNA was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Akt, GSK-3\u03b2, MMP2, \u03b2-catenin, and p53 protein expression, plus Akt, GSK-3\u03b2, and \u03b2-catenin phosphorylation, were determined by Western blot.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>T24 cell proliferation, MMP2 expression, Akt ser473 and thr308 phosphorylation, GSK3\u03b2 tyr216 phosphorylation, and \u03b2-catenin ser45\/thr41 phosphorylation were all decreased by APF, whereas p53 expression, and \u03b2-catenin ser33,37\/thr41 phosphorylation, were increased by APF treatment in non-electroporated and non-target siRNA-transfected cells. Neither mRNA nor total protein expression of Akt, GSK3\u03b2, or \u03b2-catenin changed in response to APF in these cells. In addition, the changes in cell proliferation, MMP2\/p53 mRNA and protein expression, and Akt\/GSK3\u03b2\/\u03b2-catenin phosphorylation in response to APF treatment were all specifically abrogated following CKAP4 siRNA knockdown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Synthetic <jats:italic>as<\/jats:italic>-APF inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor. The mechanism for this inhibition involves regulating phosphorylation of specific cell signaling molecules (Akt, GSK3\u03b2, and \u03b2-catenin) plus mRNA and protein expression of p53 and MMP2.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-9966-29-160","type":"journal-article","created":{"date-parts":[[2011,1,5]],"date-time":"2011-01-05T19:14:21Z","timestamp":1294254861000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells"],"prefix":"10.1186","volume":"29","author":[{"given":"Hanief M","family":"Shahjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher R","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Ou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K","family":"Keay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,12,10]]},"reference":[{"key":"407_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3322\/canjclin.57.1.43","volume":"57","author":"A Jemal","year":"2007","unstructured":"Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ: Cancer statistics, 2007. 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