Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas

Abstract

Protein tyrosine phosphatase (PTPase) dephosphorylation and protein tyrosine kinase (PTKs) phosphorylation of key signal transduction proteins may be regulated by extracellular signals, making PTPases important in the regulation of cell proliferation. Leucocyte common antigen (LAR), a receptor-like PTPase, consists of E-subunit, containing the cell adhesion molecule-like receptor region, and P-subunit specific for a short segment of the extracellular region, the transmembrane peptide, and two cytoplasmic PTPase domains. We produced a monoclonal antibody against the LAR P-subunit for immunohistochemical screening of LAR expression in normal and tumourous tissues. Gliomas and gastric, colorectal, lung, breast and prostate cancers showed weak and relatively infrequent expression. Intense and diffuse expression, however, was detected in 95% (227 out of 239) of thyroid carcinomas, but only 12% (22 out of 128) of adenomas and no cases of benign thyroid disease were immunopositive. In contrast to broad staining in carcinomas, LAR expression in thyroid adenomas was often found in small focal or locally invasive areas. Western blot analysis similarly detected LAR P-subunit protein in thyroid carcinomas, but not in normal tissues. We believe this to be the first demonstration of LAR overexpression in thyroid carcinoma and may help to elucidate the role of PTPases in the development of malignancy.

c-Jun NH2 Terminal Kinase Activation and Decreased Expression of Mitogen-Activated Protein Kinase Phosphatase-1 Play Important Roles in Invasion and Angiogenesis of Urothelial Carcinomas

“…48 -50 In addition, recent reports demonstrated that JNK activation sensitizes cancer cells including urothelial carcinomas to anticancer drug-induced cytotoxicity. 15,37,51 The studies emphasized anti-tumor functions of JNK, which seem to be inconsistent with our present results. There are no critical explanations for this discrepancy, but Igaki and colleagues 52 found that JNK activation switches its proapoptotic effects to survival effects on tumor cells in the presence of oncogenic Ras in Drosophila genetic models.…”

“…Statistical analyses were performed using the Fisher's exact test supplemented by the Bonferroni procedures as described previously. 37 Results were considered significant if the P was Ͻ0.05.…”

High Expression of a New Marker PCA-1 in Human Prostate Carcinoma

“…Briefly, cell lysates were resolved by 10% SDS-PAGE and then transferred to a nitrocellulose membrane (Schleicher & Schuell, Keene, NH). The membrane was blocked with 3% bovine serum albumin in TBS-T [20 mmol/L Tris-HCl (pH 8.0), 137 mmol/L NaCl, and 0.1% Tween 20], incubated with 0.2 Ag/mL anti-PCA-1 antisera at room temperature for 1 hour, and washed thrice with TBS-T. To detect antibody binding, the membrane was exposed to horseradish peroxidase -conjugated anti-rabbit IgG (Santa Cruz Biotech, Santa Cruz, CA) diluted in TBS-T and incubated at room Immunohistochemical analysis of the expression of PCA-1 protein in paraffin-embedded sections of benign prostatic hyperplasia and prostate tumor samples was done as described previously (22). The relative degree of immunostaining was recorded as (À) when <20% of tumor cells were positive, (+) when >20% but <50% of tumor cells were positive, and (++) when over 50% of tumor cells were positive.…”

Immunohistochemical Analysis of Neuroendocrine Differentiation in Prostate Cancer

“…Because a cancer stem cell theory has recently been proposed for many malignancies, including PC, we also examined the HNE cases for any association between the presence of stem cells or progenitor cells and NE differentiation using nestin, an intermediate filament protein. The procedure of immunohistochemical staining has been previously described [19] . The antibodies and their conditions are listed in table 2 .…”