All issues > Volume 44(6); 2001

Original Article

J Korean Pediatr Soc. 2001;44(6):654-663. Published online June 15, 2001.

Anti-angiogenesis and Anti-metastasis Characteristics of the Novel Tumor Suppressor Gene PTEN

Pyoung Han PH Hwang¹, Ho Keun HK Yi¹, Myoung Hee MH Han¹, Dae Yeol DY Lee², Dae Yeol DY Lee¹, Jung Soo JS Kim¹

¹Department of Pediatrics, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonju, Korea
²School of Life Science*, Jeonju University, Chonju, Korea

Abstract

Purpose
: The tumor suppressor gene PTEN/MMAC1 is mutated in a variety of advanced and metastatic cancers, strongly suggesting that PTEN/MMAC1 alterations may be involved in tumor progression and the formation of metastases. However, the roles of PTEN in tumor growth and metastasis and its functional mechanisms are not fully understood. We evaluated the tumor suppressor function of PTEN/MMAC1 gene on tumor growth, angiogenesis and metastasis in vitro and in vivo.
Methods
: Exogenous PTEN expression were analyzed by Western immunoblot or Northern blot analysis. To investigate whether PTEN expression can affect the tumorigenicity of B16F10 cells, we examined the in vitro growth of PTEN-expressing B16F10 cells in soft agar and in vivo growth of these cells in C57BL/6 mice. We also investigated whether PTEN expression influences the formation of experimental pulmonary metastasis of B16F10 melanoma cells in C57BL/6 mice. For further insight into the mechanisms underlying the PTEN-mediated inhibition of tumor metastasis, we examined the role of PTEN on the angiogenesis, using the chorioallantoic membrane (CAM) assay, and the activity of MMPs, using gelatine zymography.
Results
: Our results from in vitro and in vivo assays showed that PTEN/MMAC1 inhibited the tumorigenicity of B16F10 melanoma cells. The anti-metastatic function of PTEN/MMAC1 was also demonstrated in our experimental pulmonary metastatic animal model. Furthermore, PTEN/MMAC1 significantly inhibited neovascularization in chicken embryo and lowered MMPs secretion.
Conclusion
: These data suggest that the PTEN tumor suppressor protein inhibits tumorigenicity and metastasis through inhibition of angiogenesis and regulation of MMP expression.

Keywords :PTEN/MMAC1, Tumorigenicity, Anti-metastasis, Anti-angiogenesis