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 characterized 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 normal mammary gland and over-expressed in aggressive mammary tumors.


METHODS
We have investigated the expression of axl immunohistochemically 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 epithelial cells. Axl protein shows membrane associated staining in high correlation (P = 0.004) with the expression of the estrogen receptor (ER). Axl expression was found in a subset of breast carcinomas and was also correlated with high significance (P < 0.0001) with the presence of ER.


CONCLUSIONS
Our results suggest that axl may serve as a mediator of estrogen stimulation preventing the completion of the breast epithelial life cycle and that estrogen induced axl expression may give a survival signal to cancerous cells, preventing them from dying through apoptosis.
Berclaz
G
G
Department of Obstetrics and Gynecology, University Hospital, Berne, Switzerland. gilles.berclaz@insel.ch
Altermatt
H J
HJ
Rohrbach
V
V
Kieffer
I
I
Dreher
E
E
Andres
A C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000378:metabolism*; D017698:Postmenopause / Q000378:metabolism; D017697:Premenopause / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013223:Statistics as Topic; D000094963:Axl Receptor Tyrosine Kinase
D015415:Biomarkers; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human