Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.35 (
matrix metalloproteinase 9
)
2,207
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have examined the effect that cell shape has on production of the
92-kDa gelatinase
B, an enzyme of the matrix metalloproteinase family thought to contribute to the invasiveness of both normal and malignant cells. Using the agent poly(
HEMA
) and a human melanoma cell line that constitutively produces both the 72- and 92-kDa gelatinases, we have found that alteration in cell shape, that is, a change in cell "roundness," resulted in a specific loss of the constitutive production of the
92-kDa gelatinase
B. To examine this phenomenon further, cells were treated with an inhibitor of actin polymerization, cytochalasin D. This treatment also resulted in a loss of
92-kDa gelatinase
B production, provided the cells were treated with drug from the out-set of the experiment. If the cells were allowed to attach and spread prior to drug exposure, no loss of
92-kDa gelatinase
B production was observed. Similar to the poly (
HEMA
) results, cytochalasin D had little effect on production of the 72-kDa gelatinase A. Treatment with the tubulin polymerization inhibitor colchicine had no effect on
92-kDa gelatinase
B production, nor did growth of the cells as three-dimensional tumor spheroids, although an alteration in cell morphology was observed in both instances. This phenomenon was studied in another system, namely, HL-60 cells, which were induced to differentiate into macrophage-like cells in response to TPA treatment and consequently produce the
92-kDa gelatinase
B. HL-60 cells treated with TPA and cytochalasin D failed to produce the
92-kDa gelatinase
B. These results suggest that the
92-kDa gelatinase
B can be regulated by alterations in cell shape but more specifically, by alterations in the organization of the actin cytoskeleton. Furthermore, the mechanism responsible for cell shape/actin cytoskeletal down-regulation of the
92-kDa gelatinase
B may be common to many cell types competent to produce this enzymatic activity.
...
PMID:Constitutive production of 92-kDa gelatinase B can be suppressed by alterations in cell shape. 779 86