The Ret receptor tyrosine kinase pathway functionally interacts with the ERalpha pathway in breast cancer.
A limited number of receptor tyrosine kinases (e.g., ErbB and fibroblast growth factor receptor families) have been genetically linked to breast cancer development. Here, we investigated the contribution of the Ret receptor tyrosine kinase to breast tumor biology. Ret was expressed in primary breast tumors and cell lines. In estrogen receptor (ER)alpha-positive MCF7 and T47D lines, the ligand (glial-derived neurotrophic factor) activated signaling pathways and increased anchorage-independent proliferation in a Ret-dependent manner, showing that Ret signaling is functional in breast tumor cells. Ret expression was induced by estrogens and Ret signaling enhanced estrogen-driven proliferation, highlighting the functional interaction of Ret and ER pathways. Furthermore, Ret was detected in primary cancers, and there were higher Ret levels in ERalpha-positive tumors. In summary, we showed that Ret is a novel proliferative pathway interacting with ER signaling in vitro. Expression of Ret in primary breast tumors suggests that Ret might be a novel therapeutic target in breast cancer.
Boulay
Anne
A
Friedrich Miescher Institute for BioMedical Research, Basel, Switzerland.
Breuleux
Madlaina
M
Stephan
Christine
C
Fux
Caroline
C
Brisken
Cathrin
C
Fiche
Maryse
M
Wartmann
Markus
M
Stumm
Michael
M
Lane
Heidi A
HA
Hynes
Nancy E
NE
D000362:Agar / Q000737:chemistry; D001706:Biopsy; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism
D047628:Estrogen Receptor alpha; D051100:Glial Cell Line-Derived Neurotrophic Factor; D013256:Steroids; D000362:Agar; D051096:Proto-Oncogene Proteins c-ret