First Author | Leco KJ | Year | 1992 |
Journal | Gene | Volume | 117 |
Issue | 2 | Pages | 209-17 |
PubMed ID | 1639268 | Mgi Jnum | J:1706 |
Mgi Id | MGI:50232 | Doi | 10.1016/0378-1119(92)90731-4 |
Citation | Leco KJ, et al. (1992) Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts. Gene 117(2):209-17 |
abstractText | A cDNA containing the complete coding region of the murine tissue inhibitor of metalloproteinases-2 (TIMP-2) was isolated using reverse transcription-polymerase chain reaction amplification. The predicted murine TIMP-2 amino acid sequence shows 96% identity with human TIMP-2, but only 42% identity with murine TIMP-1. This high degree of evolutionary conservation between the human and mouse proteins suggests that TIMP-2 performs an essential biological function. The expression of the TIMP-1 and TIMP-2 mRNAs was examined in normal and ras-transformed murine fibroblasts. While TIMP-1 transcription was highly serum-inducible in normal murine C3H10T1/2 fibroblasts, TIMP-2 mRNA expression was largely constitutive. A series of ras-transformed derivatives of C3H10T1/2 fibroblasts showed great variability in TIMP-1 expression: some lines retained serum inducibility, others displayed constitutive expression at either high or low levels. In contrast, TIMP-2 expression was insensitive to transformation. Neither TIMP-1 nor TIMP-2 expression at the RNA level, or total TIMP activity in conditioned media could be correlated with the metastatic potential of the ras-transformed lines. Our data demonstrate that the mechanisms that regulate murine TIMP-1 and TIMP-2 expression are distinct arguing for different physiological roles for the two TIMPs. |