Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1 gene

PTEN/MMAC1/TEP1 (PTEN) is a tumor suppressor gene that is mutated in a vari ety of advanced and metastatic cancers, strongly suggests that PTEN alterat ion is possibly involved in the tumor progression and formation of metastas es. However, the roles of PTEN in tumor growth and metastasis and its funct ional mechanisms are not fully understood. We evaluated the tumor suppresso r function of PTEN gene on tumor growth and metastasis in vitro and in vivo . Our results of in vitro soft agar assay and in vivo PTEN-expressing tumor cell growth showed that PTEN inhibited the tumorigenicity of B16F10 melano ma cells. Anti-metastatic function of PTEN was also revealed by experimenta l pulmonary metastatic animal model. For the further insight into the mecha nisms underlying the PTEN-mediated inhibition of tumor metastasis, we have examined the role of PTEN on the secretion of matrix metalloproteinases (MM Ps), insulin-like growth factors (IGFs) and the expression of secretory and cellular vascular endothelial growth factor (VEGF) proteins that have been described to contribute to the metastasis of tumor. PTEN significantly low ered MMPs and IGFs secretion and also expression of secretory and cellular VEGF proteins. These results suggest that PTEN tumor suppressor protein inh ibits tumorigenicity and metastasis through regulation of MMP, IGFs, and VE GF expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.