Lysyl oxidase interacts with hormone placental lactogen and synergistically promotes breast epithelial cell proliferation and migration.
Lysyl oxidase (LOX), an extracellular amine oxidase, catalyzes the cross-linking of collagen and elastin. LOX has been also shown to play an essential role in promoting the invasive and metastatic potential of breast tumor cells. However, the LOX-interacting factors in these processes are not known. In this study, we identified placental lactogen (PL), a member of the growth hormone/prolactin hormone family, as a LOX-interacting partner using yeast two-hybrid screens. PL is normally only expressed in placental syncytiotrophoblasts, but PL genes are amplified and expressed in a high percentage of invasive ductal breast carcinomas. We confirmed LOX-PL interactions using far Western and solid phase binding assays. In activity assays, PL was not a substrate or inhibitor of LOX. We further demonstrated that PL is expressed in breast tumor epithelial cells and detected LOX-PL interactions by coimmunoprecipitation in invasive breast cancer cells. In MCF-10A normal breast epithelial cells stably expressing LOX, PL, or both, LOX had no effect on cell proliferation, PL alone increased proliferation by 49%, and coexpression of LOX and PL led to a 121% increase in cell proliferation. Unlike in tumor cells, LOX did not induce a more migratory phenotype in MCF-10A cells; nor did PL. However, their coexpression resulted in a 240% increase in cell migration, suggesting that these interactions may be highly relevant to the transition of epithelial cells toward a migratory phenotype during the development and progression of breast carcinoma and a significant role for LOX-PL interactions in epithelial cell behavior.
Polgar
Noemi
N
Cardiovascular Research Center, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96822, USA.
Fogelgren
Ben
B
Shipley
J Michael
JM
Csiszar
Katalin
K
D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D006801:Humans; D010928:Placental Lactogen / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*
D003094:Collagen; D004549:Elastin; D010928:Placental Lactogen; D008249:Protein-Lysine 6-Oxidase