PAX5alpha enhances the epithelial behavior of human mammary carcinoma cells.
Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5alpha in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5alpha was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5alpha in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of beta-CATENIN at cell-cell junctions and with altered mRNA expression of mesenchymal markers in mammary carcinoma cells. In addition, forced expression of PAX5alpha in MCF-7 and MDA-MB-231 cells significantly reduced cell migration and invasion. Concomitantly, small interfering RNA-mediated depletion of PAX5alpha increased MCF-7 total cell number, cell motility, migration, and invasion. These studies show that PAX5alpha enhances the epithelial characteristics of mammary carcinoma cells, reminiscent of mesenchymal to epithelial transition.
Vidal
Laurent J-P
LJ
The Liggins Institute, The University of Auckland, Auckland, New Zealand.
Perry
Jo K
JK
Vouyovitch
Cecile M
CM
Pandey
Vijay
V
Brunet-Dunand
Severine E
SE
Mertani
Hichem C
HC
Liu
Dong-Xu
DX
Lobie
Peter E
PE
D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D054337:Cell Dedifferentiation / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015415:Biomarkers; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D051176:beta Catenin