Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 2005 Jan 27;24(5):746-60
Date
12/14/2004Pubmed ID
15592524DOI
10.1038/sj.onc.1208203Scopus ID
2-s2.0-13444263403 (requires institutional sign-in at Scopus site) 172 CitationsAbstract
Signal transducer and activator of transcription-5 (Stat5) mediates prolactin (PRL)-induced differentiation and growth of breast epithelial cells. We have recently identified active Stat5 as a tumor marker of favorable prognosis in human breast cancer, and determined that Stat5 activation is lost during metastatic progression. Here we provide novel evidence for an invasion-suppressive role of Stat5 in human breast cancer. Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo. Inducible E-cadherin was blocked by dominant-negative (Dn) Stat5 or Dn-Jak2, but not by Dn-Stat3. Further experimental data indicated a role of Stat5 as a coordinate regulator of additional invasion-related characteristics of human breast cancer cells, including cell surface association of beta-catenin, homotypic cell clustering, invasion through Matrigel, cell migration, and matrix metalloproteinase activity. A role of Stat5 as a suppressor of breast cancer invasion and metastatic progression provides a biological mechanism to explain the favorable prognosis associated with active Stat5 in human breast cancer.
Author List
Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT, Rui HMESH terms used to index this publication - Major topics in bold
AnimalsBreast Neoplasms
Cadherins
Cell Adhesion
Cell Line, Tumor
Cell Movement
Cytoskeletal Proteins
DNA-Binding Proteins
Female
Humans
Mice
Milk Proteins
Neoplasm Invasiveness
Neoplasm Metastasis
Prognosis
Prolactin
Recombinant Proteins
STAT5 Transcription Factor
Trans-Activators
Transfection
Tumor Suppressor Proteins
beta Catenin
