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

Hwang, Pyoung Han; Yi, Ho Keun; Han, Myoung Hee; Lee, Dae Yeol; Lee, Dae Yeol; Kim, Jung Soo

Original Article

Journal of the Korean Pediatric Society 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 Hwang¹, Ho Keun Yi¹, Myoung Hee Han¹, Dae Yeol Lee², Dae Yeol Lee¹, Jung Soo Kim¹

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

새로운 암억제유전자 PTEN의 항신생혈관 생성 및 항전이 특성

황평한^¹^, 이호근^¹^, 한명희^¹^, 남상윤^²^, 이대열^¹^, 김정수^¹

^¹전북대학교 의과대학 소아과학교실, 임상의학연구소
^²전주대학교 생명과학부

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.

Key Words: PTEN/MMAC1, Tumorigenicity, Anti-metastasis, Anti-angiogenesis