Expression of E1AF, an ets-oncogene transcription factor, highly correlates with malignant phenotype of malignant melanoma through up-regulation of the membrane-type-1 matrix metalloproteinase gene.
Matrix metalloproteinase (MMP) is closely involved in the degradation of extracellular matrix and confers invasive and metastatic potential to malignant tumors. MMP-2 is a type-IV collagenase secreted as a proenzyme that is activated on the surface of the tumor cell by membrane-type 1-MMP (MT1-MMP). MT1-MMP plays a critical role during tumor progression and metastasis. We investigated the expression levels of E1AF and MT1-MMP in malignant melanoma cell lines and specimens from patients in order to clarify the mechanisms responsible for the invasion and metastasis of malignant melanoma. High levels of E1AF and MT1-MMP mRNA expression were observed in melanoma cells by Northern blotting and real-time PCR. The expression level was highly correlated with an invasive potential determined by an in vitro invasion assay. The down-regulation of MT1-MMP was identified when E1AF was knocked down by RNA interference. These results suggest that E1AF plays a crucial role in the invasion and metastasis of malignant melanoma through up-regulating the MT1-MMP expression.
Hata
Hironobu
H
Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
Kitamura
Tetsuya
T
Higashino
Fumihiro
F
Hida
Kyoko
K
Yoshida
Koichi
K
Ohiro
Yoichi
Y
Totsuka
Yasunori
Y
Kitagawa
Yoshimasa
Y
Shindoh
Masanobu
M
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis* / Q000502:physiology*; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D011509:Proteoglycans / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis* / Q000502:physiology*; D034622:RNA Interference; D015854:Up-Regulation
D017500:Adenovirus E1A Proteins; D004338:Drug Combinations; C079853:ETV4 protein, human; D007797:Laminin; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C059485:matrigel; D003094:Collagen; D053511:Matrix Metalloproteinase 14