Overexpression of caveolin-1 in adult T-cell leukemia

Caveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1–infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1– positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-B and cAMP response element binding protein signal pathways. HTLV-1– infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor (TGF-)–induced growth inhibition. Caveolin-1 was colocalized with TGF- type I receptor in HTLV-1–infected T-cell lines and suppressed TGF- signaling. Caveolin-1 knockdown in an HTLV-1– infected T-cell line exhibited susceptibility to TGF-. Thus, we describe a new function for Tax, repression of TGFsignaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis. (Blood. 2010;115: 2220-2230)