PROLACTIN STIMULATES THE JAK2 AND FECAL ADHESION KINASE PATHWAYS IN HUMAN BREAST-CARCINOMA T47-D CELLS

Treatment of T47-D human breast carcinoma cells with recombinant prola ctin (rhPRL) induced a concentration- and time-dependent increase in t he phosphotyrosine content of JAK2. rhPRL also stimulated JAK2 tyrosin e phosphorylation more weakly in three other breast carcinoma lines, M CF-7, ZR-75-1 and MDB-MB-231. Furthermore it stimulated tyrosine phosp horylation of two isoforms of the transcriptional activator STAT5, STA T5a and STAT5b. Surprisingly, rhPRL treatment of T47-D cells also stim ulated tyrosine phosphorylation of focal adhesion kinase (FAK), as det ermined by immunoprecipitation with anti-phosphotyrosine antibody foll owed by immunoblotting with a specific FAK antibody. The effect of rhP RL was rapid and concentration-dependent, being maximal at 5 ng/ml. At rhPRL concentrations above 25 ng/ml, FAK tyrosine phosphorylation dec lined but remained above control levels at 100 ng/ml. rhPRL also stimu lated paxillin tyrosine phosphorylation in T47-D cells with similar co ncentration- and time-dependence. In a second human breast carcinoma c ell line, MCF-7, rhPRL produced very similar effects on FAK and paxill in tyrosine phosphorylation. These findings identify a new protein tyr osine kinase pathway in the action of the lactogenic hormone rhPRL and represent the first report that a hormone acting through a member of the haemopoietin receptor super-family can regulate the FAK/paxillin p athway.