Leukocyte common antigen-related tyrosine phosphatase receptor: increased expression and neuronal-type splicing in breast cancer cells and tissue

Abstract

The findings that protein tyrosine phosphatases (PTPs) regulate cell proliferation, response to growth factors, and cellular adhesion and the discovery that mutations in PTP genes are associated with breast cancer suggest that altered expression of PTPs contributes to the breast cancer cell phenotype. The leukocyte common antigen-related (LAR) PTP receptor is a prototype member of the class of PTP receptors containing cell adhesion domains. Full-length constitutively spliced LAR transcripts are expressed in breast and other tissues, whereas alternatively spliced isoforms are preferentially expressed in the nervous system. As a first step in evaluating the hypothesis that LAR-type PTPs influence breast cancer cell behavior, LAR expression and neuronal-type alternative splicing were examined in normal and breast cancer cell lines and tissues. Northern blot analysis demonstrated markedly increased LAR mRNA levels in breast cancer cell lines and tissues. Western blot analysis showed a greater than tenfold increase in LAR protein levels in breast cancer tissues. Reverse transcription-polymerase chain reaction was used to assess alternative splicing of extracellular and proximal membrane exons. Differential patterns of extracellular alternative splicing were found in normal versus carcinoma cell lines and tissues. Western blot analysis demonstrated increased levels of LAR protein isoforms encoded by alternatively spliced transcripts in breast cancer cell lines. This study is the first demonstration of increased LAR mRNA and LAR protein expression in breast cancer tissue and nontransformed cell lines and helps to elucidate the role of LAR in human breast cancer. The differential patterns of alternative splicing of LAR transcripts introduce LAR isoforms as candidate markers for future studies correlating differential gene expression and tumor behavior.