Pleiotrophin (PTN, Ptn) is an 18kDa
cytokine expressed in human breast
cancers. Since inappropriate expression of Ptn stimulates progression of
breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human
breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in
breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive
breast cancer phenotype.
Pleiotrophin signals by inactivating its receptor, the receptor
protein tyrosine phosphatase (RPTP)beta/zeta, and, recently, PTN was found to activate
anaplastic lymphoma kinase (ALK) through the PTN/
RPTPbeta/zeta signaling pathway in PTN-stimulated cells, not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant
cancers and activated ALK is a potent oncogenic
protein, we examined human breast
cancers to test the possibility that ALK may be expressed in breast
cancers and potentially activated through the PTN/
RPTPbeta/zeta signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human
breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the ;;dotted" pattern characteristic of ALK fusion
proteins in
anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast
cancers and potentially activated either through the PTN/
RPTPbeta/zeta signaling pathway, or, alternatively, as an activated fusion
protein to stimulate progression of
breast cancer in humans.