title: PTEN overexpression improves cisplatin-resistance of human ovarian cancer cells through upregulating KRT10 expression.
abstract: Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the downstream molecules of PTEN involved in the resistance-reversing effect have not been completely clarified. Therefore, we screened the downstream molecules of PTEN and studied their interactions in C13K ovarian cancer cells using a 3D culture model. Firstly, we constructed an ovarian cancer cell line stably expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we examined the differently expressed proteins that interacted with PTEN in C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation. KRT10 was identified as a differently expressed protein in cisplatin-treated C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced KRT10 overexpression may also act as a therapeutic method for overcoming MDR in ovarian cancer.
authors.affiliation: Department of Gynecological Oncology, Tianjin Medial University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, PR China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Gynecological Oncology, Tianjin Medial University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Gynecological Oncology, Tianjin Medial University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, PR China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Gynecological Oncology, Tianjin Medial University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, PR China. Electronic address: quan_haotj@126.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053550:Keratin-10 / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C507493:KRT10 protein, human; D053550:Keratin-10; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002945:Cisplatin
keywords: Cisplatin; KRT10; Multi-drug resistance; Ovarian cancer; PTEN