Expression of the tissue inhibitor of metalloproteinases (TIMP) gene family in normal and osteoarthritic joints

1999 ◽  
Vol 18 (5-6) ◽  
pp. 183-191 ◽  
Author(s):  
S. Su ◽  
J. Grover ◽  
P. J. Roughley ◽  
J. A. DiBattista ◽  
J. Martel-Pelletier ◽  
...  
Keyword(s):  
Gene Family ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Timp Gene

scholarly journals Increased erythroid potentiating activity/tissue inhibitor of metalloproteinases and jun/fos transcription factor complex characterize tumor promoter-induced megakaryoblastic differentiation of K562 leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1974-1982 ◽  
Author(s):  
R Alitalo ◽  
J Partanen ◽  
L Pertovaara ◽  
E Holtta ◽  
L Sistonen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Northern Hybridization ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Fold Induction ◽  
Transcription Factor Complex ◽  
Timp Gene

Abstract Molecular cloning has revealed that erythroid potentiating activity (EPA) and tissue inhibitor of metalloproteinases (TIMP) represent two distinct activities of a single protein. We have studied the expression of the EPA/TIMP gene at the mRNA and protein levels during 12-O- tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryoblastic differentiation of K562 human chronic myeloid leukemia cells. Northern hybridization analysis showed that the EPA/TIMP mRNA was increased within 3 hours of TPA-induction and reached maximal levels (about 50- fold induction) during the first day of treatment. The expression of mRNAs for two major metalloproteinases, collagenase-I and stromelysin, were activated in parallel in the differentiation-induced K562 cells. The increase of EPA/TIMP mRNA correlated with increased EPA/TIMP protein biosynthesis and secretion: the TPA-induced cells secreted substantially enhanced amounts of metabolically labeled proteins, of which EPA/TIMP represented up to 50% after the first day of treatment (over 100-fold induction). The induction of EPA/TIMP mRNA was associated with its increased transcription. EPA/TIMP induction required continuous protein synthesis, being completely inhibited by addition of the protein synthesis inhibitor cycloheximide simultaneously with TPA, but only partially inhibited in a time- dependent manner if cycloheximide was added after TPA. Unlike in other cells tested, the jun and c-fos transcription factor mRNAs showed a prolonged biphasic induction response in K562 cells during TPA treatment. This response was associated with enhanced activity of a transfected recombinant reporter plasmid containing binding sites for the jun/fos transcription factor complex (AP-1) similar to the TPA- responsive element (TRE) sequence we found in the EPA/TIMP gene promoter. We suggest that the induction of EPA/TIMP and several other genes specific for the differentiating K562 cells may be a consequence of the sustained activation of immediate early genes encoding transcription factors, such as jun and c-fos.

scholarly journals The prognostic and diagnostic value of tissue inhibitor of metalloproteinases gene family and potential function in gastric cancer

2021 ◽  
Vol 12 (13) ◽  
pp. 4086-4098
Author(s):  
Zhao Li ◽  
Qinwen Jing ◽  
Liucheng Wu ◽  
Jiansi Chen ◽  
Mingwei Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gene Family ◽  
Potential Function ◽  
Diagnostic Value ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor

scholarly journals Increased erythroid potentiating activity/tissue inhibitor of metalloproteinases and jun/fos transcription factor complex characterize tumor promoter-induced megakaryoblastic differentiation of K562 leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1974-1982 ◽  
Author(s):  
R Alitalo ◽  
J Partanen ◽  
L Pertovaara ◽  
E Holtta ◽  
L Sistonen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Northern Hybridization ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Fold Induction ◽  
Transcription Factor Complex ◽  
Timp Gene

Molecular cloning has revealed that erythroid potentiating activity (EPA) and tissue inhibitor of metalloproteinases (TIMP) represent two distinct activities of a single protein. We have studied the expression of the EPA/TIMP gene at the mRNA and protein levels during 12-O- tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryoblastic differentiation of K562 human chronic myeloid leukemia cells. Northern hybridization analysis showed that the EPA/TIMP mRNA was increased within 3 hours of TPA-induction and reached maximal levels (about 50- fold induction) during the first day of treatment. The expression of mRNAs for two major metalloproteinases, collagenase-I and stromelysin, were activated in parallel in the differentiation-induced K562 cells. The increase of EPA/TIMP mRNA correlated with increased EPA/TIMP protein biosynthesis and secretion: the TPA-induced cells secreted substantially enhanced amounts of metabolically labeled proteins, of which EPA/TIMP represented up to 50% after the first day of treatment (over 100-fold induction). The induction of EPA/TIMP mRNA was associated with its increased transcription. EPA/TIMP induction required continuous protein synthesis, being completely inhibited by addition of the protein synthesis inhibitor cycloheximide simultaneously with TPA, but only partially inhibited in a time- dependent manner if cycloheximide was added after TPA. Unlike in other cells tested, the jun and c-fos transcription factor mRNAs showed a prolonged biphasic induction response in K562 cells during TPA treatment. This response was associated with enhanced activity of a transfected recombinant reporter plasmid containing binding sites for the jun/fos transcription factor complex (AP-1) similar to the TPA- responsive element (TRE) sequence we found in the EPA/TIMP gene promoter. We suggest that the induction of EPA/TIMP and several other genes specific for the differentiating K562 cells may be a consequence of the sustained activation of immediate early genes encoding transcription factors, such as jun and c-fos.

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