Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast

Background: Axl, a member of a family of receptor tyrosine kinases characte rized by an extracellular domain resembling cell adhesion molecules and an intracellular conserved tyrosine kinase domain has been reported to induce cell proliferation and transformation. In mice, axl is expressed in the nor mal mammary gland and over-expressed in aggressive mammary tumors. Patients and methods: We have investigated the expression of axl immunohist ochemically in 23 normal human breast samples and in 111 consecutive breast carcinomas. Expression of axl was correlated with tumour characteristics ( lymph node involvement, stage, grade) and immunohistochemical expression of ER, PR, Ki-67 and c-erbB-2. Results: In normal tissue, axl localizes to the membrane of breast epitheli al cells. Axl protein shows membrane associated staining in high correlatio n (P = 0.004) with the expression of the estrogen receptor (ER). Axl expres sion was found in a subset of breast carcinomas and was also correlated wit h high significance (P < 0.0001) with the presence of ER. Conclusion: Our results suggest that axl may serve as a mediator of estroge n stimulation preventing the completion of the breast epithelial life cycle and that estrogen induced axl expression may give a survival signal to can cerous cells, preventing them from dying through apoptosis.