The receptor protein tyrosine phosphatase (RPTP)beta/zeta is expressed in different subtypes of human breast cancer.
Increasing evidence suggests mutations in human breast cancer cells that induce inappropriate expression of the 18-kDa cytokine pleiotrophin (PTN, Ptn) initiate progression of breast cancers to a more malignant phenotype. Pleiotrophin signals through inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP)beta/zeta, leading to increased tyrosine phosphorylation of different substrate proteins of RPTPbeta/zeta, including beta-catenin, beta-adducin, Fyn, GIT1/Cat-1, and P190RhoGAP. PTN signaling thus has wide impact on different important cellular systems. Recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTPbeta/zeta signaling pathway; this discovery potentially is very important, since constitutive ALK activity of nucleophosmin (NPM)-ALK fusion protein is causative of anaplastic large cell lymphomas, and, activated ALK is found in other malignant cancers. Recently ALK was identified in each of 63 human breast cancers from 22 subjects. We now demonstrate that RPTPbeta/zeta is expressed in each of these same 63 human breast cancers that previously were found to express ALK and in 10 additional samples of human breast cancer. RPTPbeta/zeta furthermore was localized not only in its normal association with the cell membrane but also scattered in cytoplasm and in nuclei in different breast cancer cells and, in the case of infiltrating ductal carcinomas, the distribution of RPTPbeta/zeta changes as the breast cancer become more malignant. The data suggest that the PTN/RPTPbeta/zeta signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer.
Perez-Pinera
Pablo
P
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Garcia-Suarez
Olivia
O
Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto Universitario de Oncologia del Principado de Asturias, Oviedo, Spain.
Menendez-Rodriguez
Primitiva
P
Hospital Universitario Central de Asturias, Oviedo, Spain.
Mortimer
J
J
Moore's Cancer Center, University of California San Diego, San Diego, CA, USA.
Chang
Y
Y
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Astudillo
A
A
Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto Universitario de Oncologia del Principado de Asturias, Oviedo, Spain.
Deuel
T F
TF
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: tfdeuel@scripps.edu.
D000230:Adenocarcinoma / Q000378:metabolism; D000077548:Anaplastic Lymphoma Kinase; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D000078792:Midkine; D008954:Models, Biological; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D015398:Signal Transduction; D014018:Tissue Distribution
D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin; D000078792:Midkine; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
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