Prolactin Stimulates the JAK2 and Focal Adhesion Kinase Pathways in Human Breast Carcinoma T47-D Cells
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Treatment of T47-D human breast carcinoma cells with recombinant prolactin (rhPRL) induced a concentration- and time-dependent increase in the phosphotyrosine content of JAK2. rhPRL also stimulated JAK2 tyrosine phosphorylation more weakly in three other breast carcinoma lines, MCF-7, ZR-75-1 and MDA-MB-231. Furthermore it stimulated tyrosine phosphorylation of two isoforms of the transcriptional activator STAT5, STAT5a and STAT5b. Surprisingly, rhPRL treatment of T47-D cells also stimulated tyrosine phosphorylation of focal adhesion kinase (FAK), as determined by immunoprecipitation with anti-phosphotyrosine antibody followed by immunoblotting with a specific FAK antibody. The effect of rhPRL was rapid and concentration-dependent, being maximal at 5 ng/ml. At rhPRL concentrations above 25 ng/ml, FAK tyrosine phosphorylation declined but remained above control levels at 100 ng/ml. rhPRL also stimulated paxillin tyrosine phosphorylation in T47-D cells with similar concentration- and time-dependence. In a second human breast carcinoma cell line, MCF-7, rhPRL produced very similar effects on FAK and paxillin tyrosine phosphorylation. These findings identify a new protein tyrosine 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 superfamily can regulate the FAK/paxillin pathway.
Zhang J, Liu J, Yue Y, Wang L, He Q, Xu S J Exp Clin Cancer Res. 2024; 43(1):173.
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Prolactin: The Third Hormone in Breast Cancer.
Schuler L, OLeary K Front Endocrinol (Lausanne). 2022; 13:910978.
PMID: 35784527 PMC: 9244687. DOI: 10.3389/fendo.2022.910978.
The Relevant Participation of Prolactin in the Genesis and Progression of Gynecological Cancers.
Ramirez-de-Arellano A, Villegas-Pineda J, Hernandez-Silva C, Pereira-Suarez A Front Endocrinol (Lausanne). 2021; 12:747810.
PMID: 34745013 PMC: 8566755. DOI: 10.3389/fendo.2021.747810.
Leehy K, Truong T, Mauro L, Lange C J Steroid Biochem Mol Biol. 2017; 176:88-93.
PMID: 28442393 PMC: 5653461. DOI: 10.1016/j.jsbmb.2017.04.011.
Barcus C, OLeary K, Brockman J, Rugowski D, Liu Y, Garcia N Breast Cancer Res. 2017; 19(1):9.
PMID: 28103936 PMC: 5244528. DOI: 10.1186/s13058-017-0801-1.