Leukocyte common-antigen-related tyrosine phosphatase receptor: altered expression of mRNA and protein in the New England Deaconess Hospital rat lineexhibiting spontaneous pheochromocytoma

Regulation of cell proliferation by protein tyrosine phosphatases (PTPs) su ggests that PTPs are important tumor suppressor genes. The gene encoding th e leukocyte common-antigen-related (LAR) PTP receptor maps to chromosome 1p 32-33, a region in which loss of heterozygosity is associated with human ph eochromocytoma and other neuroectodermal tumors. The rat pheochromocytoma P C12 cell line was originally derived from the transplantable P259 tumor ori ginating from the New England Deaconess Hospital (NEDH) line of Wistar inbr ed rats. Compared with their Wistar counterparts, 1-2-year-old NEDH rats ex hibit a high incidence of spontaneous pheochromocytomas, This study investi gates whether levels of LAR transcripts and protein are altered in NEDH adr enal tissue prior to tumor onset. In addition, alternative splicing of an L AR extracellular domain [LAR alternatively spliced element-c (LASE-c)], reg ulating LAR interaction with extracellular matrix components, was examined, These changes in LAR expression and alternative splicing were hypothesized to be more pronounced in tumor tissue and PC12 cells. Northern blot analys is demonstrated the presence of the similar to 5 kb LAR transcript in all c ell lines examined, except PC12, In adrenal medulla tissue harvested from 2 -3-month-old rats, LAR similar to 8 and similar to 5 kb transcript expressi on was decreased in NEDH compared with Wistar samples. RT-PCR demonstrated increased splicing of the LASE-c 27 bp alternatively spliced insert in the] LAR extracellular domain in NEDH adrenal medulla tissue, Even greater LASE- c splicing was detected in adrenal medulla tumor tissue derived from 12-mon th-old NEDH rats and in PC12 cells. Western blot analysis demonstrated decr eased levels of LAR protein and increased levels of LASE-c containing LAR p rotein isoforms in NEDH adrenal medulla tissue. These studies demonstrate t hat patterns of altered LAR expression present in PC12 cells and in pheochr omocytoma tumor tissue are also present in adrenal tissue predisposed to a high incidence of spontaneous pheochromocytoma.