T. Yang et al., Leukocyte common antigen-related tyrosine phosphatase receptor: Increased expression and neuronal-type splicing in breast cancer cells and tissue, MOL CARCINO, 25(2), 1999, pp. 139-149
The findings that protein tyrosine phosphatases (PTPs) regulate cell prolif
eration, response to growth factors, and cellular adhesion and the discover
y that mutations in PTP genes are associated with breast cancer suggest tha
t altered expression of PTPs contributes to the breast cancer cell phenotyp
e. The leukocyte common antigen-related (LAR) PTP receptor is a prototype m
ember of the class of PTP receptors containing cell adhesion domains. Full-
length constitutively spliced LAR transcripts are expressed in breast and o
ther tissues, whereas alternatively spliced isoforms are preferentially exp
ressed in the nervous system. As a first step in evaluating the hypothesis
that LAR-type PTPs influence breast cancer cell behavior, LAR expression an
d neuronal-type alternative splicing were examined in normal and breast can
cer cell lines and tissues. Northern blot analysis demonstrated markedly in
creased LAR mRNA levels in breast cancer cell lines and tissues. Western bl
ot 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 fo
und in normal versus carcinoma cell lines and tissues. Western blot analysi
s demonstrated increased levels of LAR protein isoforms encoded by alternat
ively spliced transcripts in breast cancer cell lines. This study is the fi
rst demonstration of increased LAR mRNA and LAR protein expression in breas
t cancer tissue and nontransformed cell lines and helps to elucidate the ro
le 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
. Published 1999 Wiley-Liss, Inc.dagger.