| RRC ID |
1357
|
| 著者 |
Itano N, Sawai T, Atsumi F, Miyaishi O, Taniguchi S, Kannagi R, Hamaguchi M, Kimata K.
|
| タイトル |
Selective expression and functional characteristics of three mammalian hyaluronan synthases in oncogenic malignant transformation.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Malignant transformation of fibroblasts and epithelial cells is often accompanied by increased hyaluronan production and accumulation. Despite recent progress in the study of hyaluronan biosynthesis, the mechanisms underlying the transformation-induced overproduction of hyaluronan have not been elucidated. Here we report that activity and transcriptional levels of hyaluronan synthase (HAS) significantly increased after oncogenic malignant transformation of a rat 3Y1 fibroblast cell line. Of three HAS isoforms (HAS1, HAS2, and HAS3), only HAS2 gene expression was increased in the v-Ha-ras transformed 3Y1 cells, which show less malignancy. In contrast, both HAS1 and HAS2 expressions were elevated in the highly malignant cells transformed with v-src and/or v-fos. To assess the contribution of HAS expression to the oncogenic malignant transformation, we established stable cell transfectants expressing sense and antisense HAS genes. Antisense suppression of the HAS2 expression significantly decreased hyaluronan production in the cells transformed by the oncogenic v-Ha-ras and eventually led to a reduction in tumorigenicity in the rat peritoneum. The introduction of the HAS1 and HAS2 genes promoted the growth of subcutaneous tumors in a manner dependent on the levels of hyaluronan synthesis. Significant growth promotion was observed within a wide range of HAS1 expression. In contrast, the growth stimulation was only seen within a narrow range of HAS2 expression, and high levels of HAS2 expression even inhibited tumor growth. These results suggest that proper regulation of the expression of each HAS isoform is required for optimal malignant transformation and tumor growth.
|
| 巻・号 |
279(18)
|
| ページ |
18679-87
|
| 公開日 |
2004-4-30
|
| DOI |
10.1074/jbc.M313178200
|
| PII |
S0021-9258(19)75423-4
|
| PMID |
14724275
|
| MeSH |
Animals
Base Sequence
Cell Line, Transformed
Cell Transformation, Neoplastic / metabolism*
Gene Expression Regulation, Neoplastic*
Glucuronosyltransferase / genetics
Glucuronosyltransferase / metabolism*
Glucuronosyltransferase / physiology
Hyaluronan Synthases
Hyaluronic Acid / biosynthesis
Hyaluronic Acid / physiology
Mice
Molecular Sequence Data
Neoplasms, Experimental / etiology
Neoplasms, Experimental / pathology
Oligonucleotides, Antisense / pharmacology
RNA, Messenger / analysis
Rats
Transfection
Transferases / genetics
Transferases / metabolism
Transferases / physiology
Up-Regulation
|
| IF |
4.238
|
| 引用数 |
118
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
SV-3Y1-C66(RCB0343)
E1A-3Y1-1(RCB0332)
HR-3Y1-1(RCB0356)
HR-3Y1-2(RCB0357) |
