ErbB2 and TGF-beta: a cooperative role in mammary tumor progression?
Amplification and overexpression of ErbB2 (HER2/Neu) is one of the most common alterations associated with breast cancer. Activation of ErbB2 via homodimerization in a non-transformed human mammary epithelial cell line, MCF-10A, in basement membrane cultures leads to formation of proliferative structures that share properties with non-invasive early stage lesions. Recently, we have shown that activation of ErbB2 homodimers combined with expression of transforming growth factor (TGF)-beta induces invasive and migratory activity in MCF-10A cells. In this system, migration requires inputs from numerous cellular pathways. We discuss this data and a model for migration induced by ErbB2 and TGF-beta. Concurrent studies by other groups have also shown that ErbB2 and TGF-beta can cooperate to increase metastatic and invasive behavior in murine mammary tumors. Here we discuss these studies and the potential implications of this research on breast cancer therapeutics.
Seton-Rogers
Sarah E
SE
Harvard Medical School, Department of Cell Biology, Boston, Massachusetts 02115, USA.
Brugge
Joan S
JS
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta