Overexpression and involvement of special AT-rich sequence binding protein 1 in multidrug resistance in human breast carcinoma cells.
Special AT-rich sequence binding protein (SATB) 1 has been proposed to act as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. Here we found that SATB1 expression is upregulated in multidrug-resistant breast cancer cells that exhibit higher invasive potential than the parental cells. Apart from accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was demonstrated to confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1-overexpressing transfectants. SATB1 depletion could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in vitro and in vivo. The SATB1-induced P-glycoprotein-mediated MDR could be reversed by treatment with anti-P-glycoprotein mAb. Moreover, SATB1 plays an important role in anti-apoptotic activity in MCF7/ADR cells in response to adriamycin treatment, which suggests another mechanism contributing to SATB1-related MDR of breast cancers. These data provide new insights into the mode by which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in this process.
Li
Qing-Quan
QQ
Department of Pathology, Shanghai Medical College, Shanghai, China.
Chen
Zhong-Qing
ZQ
Xu
Jing-Da
JD
Cao
Xi-Xi
XX
Chen
Qi
Q
Liu
Xiu-Ping
XP
Xu
Zu-De
ZD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human