%0 Journal Article
%T Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer
%A Jacqueline S Biscardi
%A Rumey C Ishizawar
%A Corinne M Silva
%A Sarah J Parsons
%J Breast Cancer Research
%D 2000
%I BioMed Central
%R 10.1186/bcr55
%X Recent evidence has implicated an involvement of tyrosine kinases in human breast cancer development. Two families in particular have been examined, namely, the human epidermal growth factor and the Src families of tyrosine kinases.The human epidermal growth factor receptor (HER1) is the prototype of a family that consists of four known members (EGF receptor/HER1, neu/erbB2/HER2, erbB3/HER3, and erbB4/HER4). These receptor tyrosine kinases are characterized by an extracellular ligand-binding domain, an internal kinase domain, and a carboxyl-terminal domain that contains multiple tyrosine residues. Upon binding of EGF, HER1 dimerizes and becomes phosphorylated on these carboxyl-terminal tyrosyl residues, which in turn act as docking sites for multiple signaling proteins that contain SH2 domains. HER1 plays a variety of roles in normal development, and is found in ductal epithelial cells of normal breast tissue [1**].The link between HER1 and human cancer initally came from studies by Velu et al [2], who demonstrated that cells that overexpress HER1 become transformed when they are grown in the continuous presence of EGF. HER1 is overexpressed in a variety of human cancers, including benign skin hyperplasia, glioblastoma and cancers of the breast, prostate, ovary, liver, bladder, esophagus, larynx, stomach, colon, and lung [3*]. Approximately 30% of human breast tumors overexpress HER1, and this over-expression is correlated with a loss of estrogen responsiveness and a poorer prognosis [4,5]. Much evidence suggests that HER1 is involved in later stages of human breast cancer and may play a role in the metastatic process [6].Among the HER family members, HER2 is most closely related to HER1 [7] and has been found to be amplified in 10-35% of human breast carcinomas, an event that portends a poor disease prognosis [8**,9]. Overexpression of HER2 occurs more frequently in the early stages of breast cancer, and is therefore thought to be involved in tumor initiation and e
%K c-Src
%K epidermal growth factor receptor
%K human epidermal growth factor receptor 2/neu
%K signal transducers and activators of transcription
%K tyrosine phosphorylation
%U http://breast-cancer-research.com/content/2/3/203