Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction

In the present study, we searched for mutant PTEN transcripts in aggressive rheumatoid arthritis synovial fibroblasts (RA-SF) and studied the expressi on of PTEN in RA. By automated sequencing, no evidence for the presence of mutant PTEN transcripts was found. However, in situ hybridization on RA syn ovium revealed a distinct expression pattern of PTEN, with negligible stain ing in the lining layer but abundant expression in the sublining. Normal sy novial tissue exhibited homogeneous staining for PTEN. In cultured RA-SF, o nly 40% expressed PTEN. Co-implantation of RA-SF and normal human cartilage into severe combined immunodeficiency (SCID) mice showed only limited expr ession of PTEN, with no staining in those cells aggressively invading the c artilage. Although PTEN is not genetically altered in RA, these findings su ggest that a lack of PTEN expression may constitute a characteristic featur e of activated RA-SF in the lining, and may thereby contribute to the invas ive behaviour of RA-SF by maintaining their aggressive phenotype at sites o f cartilage destruction.