BACKGROUND.Caveolin-1 plays a regulatory role in several signaling pathways.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion ( P = 0.0180), lymph node metastasis ( P = 0.0033), lymphatic involvement ( P = 0.0104), venous involvement ( P = 0.0224), perineural involvement ( P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification ( P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival ( P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216–132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.

Over-expression of caveolin-1 is associated with lymph node metastasis and a worse prognosis after surgery in esophageal squamous cell carcinoma.