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 variety of advanced and metastatic cancers, strongly suggests that PTEN alteration is possibly involved in the tumor progression and 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 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 melanoma cells. Anti-metastatic function of PTEN was also revealed by experimental pulmonary metastatic animal model. For the further insight into the mechanisms underlying the PTEN-mediated inhibition of tumor metastasis, we have examined the role of PTEN on the secretion of matrix metalloproteinases (MMPs), 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 lowered MMPs and IGFs secretion and also expression of secretory and cellular VEGF proteins. These results suggest that PTEN tumor suppressor protein inhibits tumorigenicity and metastasis through regulation of MMP, IGFs, and VEGF expression.
Hwang
P H
PH
Department of Pediatrics, Chonbuk National University Medical School, Chonju, Chonbuk, 561-712, South Korea. hwaph@maok.chonbuk.ac.kr
Yi
H K
HK
Kim
D S
DS
Nam
S Y
SY
Kim
J S
JS
Lee
D Y
DY
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D011863:Radioimmunoassay; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D020782:Matrix Metalloproteinases