title: Skp2 is associated with paclitaxel resistance in prostate cancer cells.
abstract: Prostate cancer is the most commonly diagnosed tumor in men in the United States. Patients with hormone-refractory prostate cancer are often treated with paclitaxel, but most of them eventually develop drug resistance. S-phase kinase associated protein 2 (Skp2) is a component of the SCF (Skp1-Cullin1-F-box) type of E3 ubiquitin ligase complexes. In the present study, we investigated the role of Skp2 in paclitaxel-resistant DU145-TxR or PC-3-TxR cells by Skp2 silencing or using Skp2 inhibitors. We first confirmed that Skp2 expression is up-regulated in DU145-TxR or PC-3-TxR cells compared with their parental cells DU145 or PC-3, respectively. Knockdown of Skp2 or Skp2 inhibitor treatment in DU145-TxR or PC-3-TxR cells restored paclitaxel sensitivity. E-cadherin was decreased while Vimentin was increased in PC-3-TxR or DU145-TxR cells. In addition, p27 expression was inversely correlated with Skp2 expression in DU145-TxR or PC-3-TxR cells. Moreover, p27 was found to increase in both Skp2 silencing PC-3-TxR and DU145-TxR cells. These results suggest that Skp2 is associated with prostate cancer cell resistance to paclitaxel. Skp2 may be a potential therapeutic target for drug-resistant prostate cancer.
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yeguo
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.affiliation: Department of Urology and Pathology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017239:Paclitaxel