title: Comparative proteomic analysis of paclitaxel resistance-related proteins in human breast cancer cell lines.
abstract: Paclitaxel is widely used to treat various cancers; however, resistance to this drug is a major obstacle to breast cancer chemotherapy. To identify the proteins involved in paclitaxel resistance, the present study compared the proteomes of MCF-7 human breast cancer cells and its paclitaxel-resistant subclone MCF-7/PTX. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry, 11 upregulated and 12 downregulated proteins were identified in MCF-7/PTX cells compared with the parental cell line. These 23 proteins were functionally classified as stress-induced chaperones, metabolic enzymes and cytoskeletal proteins. The anti-apoptotic proteins, stress-70 protein, 78-kD glucose-regulated protein, peptidyl-prolylcis-transisomerase A (PPIA) and heterogeneous nuclear ribonucleoprotein H3, were also upregulated in MCF-7/PTX cells. Notably, knockdown of the stress-response chaperone PPIA using small interfering RNA in MCF-7/PTX cells restored their sensitivity to paclitaxel. These findings indicated that PPIA may have an important role in paclitaxel resistance in MCF-7/PTX cells.
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Fujioka
authors.affiliation: Department of Chemistry, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyamoto
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: Section of Breast and Endocrine Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Uchiyama
keywords: breast cancer; paclitaxel resistance; peptidyl-prolyl cis-trans isomerase A; proteome; proteomics