Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell.
The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration.
Bausero
Maria A
MA
Center for Molecular Stress Response, Boston University Medical Center and Boston University School of Medicine, Mass., USA.
Bharti
Ajit
A
Page
Diana T
DT
Perez
Kristen D
KD
Eng
Jason W-L
JW
Ordonez
Susana L
SL
Asea
Edwina E
EE
Jantschitsch
Christian
C
Kindas-Muegge
Ingela
I
Ciocca
Daniel
D
Asea
Alexzander
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference; D014162:Transfection; D014407:Tumor Cells, Cultured
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D020780:Matrix Metalloproteinase 9