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Oncotarget. 2014 Aug 15;5(15):6038-48.

PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.

Author information

1
Departments of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago IL.
2
Department of Pathology, University of Illinois at Chicago, Chicago IL.
3
Department of Surgery, Northwestern Feinberg School of Medicine, Chicago, IL.
4
Allina Health, Minneapolis, MN, USA.
5
Department of Biopharmaceutical Sciences University of Illinois at Chicago, Chicago IL.

Abstract

Protein Tyrosine kinase 6 (PTK6/BRK) is overexpressed in the majority of human breast tumors and breast tumor cell lines. It is also expressed in normal epithelial linings of the gastrointestinal tract, skin, and prostate. To date, expression of PTK6 has not been extensively examined in the normal human mammary gland. We detected PTK6 mRNA and protein expression in the immortalized normal MCF-10A human mammary gland epithelial cell line, and examined PTK6 expression and activation in a normal human breast tissue microarray, as well as in human breast tumors. Phosphorylation of tyrosine residue 342 in the PTK6 activation loop corresponds with its activation. Similar to findings in the prostate, we detect nuclear and cytoplasmic PTK6 in normal mammary gland epithelial cells, but no phosphorylation of tyrosine residue 342. However, in human breast tumors, striking PTK6 expression and phosphorylation of tyrosine 342 is observed at the plasma membrane. PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane. Understanding consequences of PTK6 activation at the plasma membrane may have implications for developing novel targeted therapies against this kinase.

PMID:
25153721
PMCID:
PMC4171611
DOI:
10.18632/oncotarget.2153
[Indexed for MEDLINE]
Free PMC Article

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