Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells.

Abstract

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.

• Authors: Ahmed S Sultan, Jianwu Xie, Matthew J LeBaron, Erica L Ealley, Marja T Nevalainen, Hallgeir Rui
• Journal: Oncogene (Oncogene) Vol. 24 Issue 5 Pg. 746-60 (Jan 27 2005) ISSN: 0950-9232 [Print] England
• PMID: 15592524 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CTNNB1 protein, human
• CTNNB1 protein, mouse
• Cadherins
• Cytoskeletal Proteins
• DNA-Binding Proteins
• Milk Proteins
• Recombinant Proteins
• STAT5 Transcription Factor
• STAT5A protein, human
• Trans-Activators
• Tumor Suppressor Proteins
• beta Catenin
• Prolactin

Topics

• Animals
• Breast Neoplasms (pathology)
• Cadherins (metabolism)
• Cell Adhesion (physiology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cytoskeletal Proteins (physiology)
• DNA-Binding Proteins (genetics, physiology)
• Female
• Humans
• Mice
• Milk Proteins (genetics)
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis
• Prognosis
• Prolactin (pharmacology)
• Recombinant Proteins (metabolism)
• STAT5 Transcription Factor
• Trans-Activators (genetics, physiology)
• Transfection
• Tumor Suppressor Proteins
• beta Catenin