The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

Pablo Perez-Pinera, Olivia Garcia-Suarez, Primitiva Menendez-Rodriguez, J. Mortimer, Y. Chang, A. Astudillo, T. F. Deuel

Research output: Contribution to journalArticlepeer-review


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)β/ζ, leading to increased tyrosine phosphorylation of different substrate proteins of RPTPβ/ζ, including β-catenin, β-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/RPTPβ/ζ 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 RPTPβ/ζ 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. RPTPβ/ζ 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 RPTPβ/ζ changes as the breast cancer become more malignant. The data suggest that the PTN/RPTPβ/ζ signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer.

Original languageEnglish (US)
Pages (from-to)5-10
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Oct 12 2007
Externally publishedYes


  • Anaplastic lymphoma kinase
  • Breast cancer
  • Midkine
  • Pleiotrophin
  • Receptor protein tyrosine phosphatase (RPTP)β/ζ
  • Tumor progression

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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