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Effect of glucocorticoids on oncogene transformed NIH3T3 cells
1Department of Tumor Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Abstract:
We studied the differential response of oncogene transformed NIH3T3 cells to glucocorticoids. As demonstrated for transformed human fibroblasts, the morphology of neu-, ras-, src- and sis-transformed mouse fibroblasts became more normal after glucocorticoid treatment. This change was not due to inhibition of the expression of oncogene mRNA or protein. However, the abl-transformed NIH3T3 cells were resistant to glucocorticoid-induced morphology change. These results indicate that the glucocorticoid-induced morphology change is specific to certain oncogene-transformed NIH3T3 cells. Transformed human fibroblasts generally have reduced amounts of cell surface fibronectin. When treated with glucocorticoids, they incorporate higher levels of fibronectin in their extracellular matrix, which correlates with their change in morphology. However, we found that, except for abl-transformed cells, the fibronectin level of the other oncogene transformed mouse cells was similar to non-transformed cells. Moreover, treatment of the neu-, ras-, src- and sis-transformed cells with glucocorticoids resulted in a change in morphology but no increase in cell surface fibronectin. These studies demonstrate that the glucocorticoid-induced morphological change of oncogene-transformed NIH3T3 cells is not due to enhanced expression of fibronectin. Therefore, other mechanisms are responsible for this glucocorticoid-induced phenotypic change of oncogene-transformed cells.
Insights
Glucocorticoids normalize the morphology of NIH3T3 cells transformed by most oncogenes, except for abl. This phenotypic change in oncogene-transformed cells is not mediated by fibronectin, suggesting alternative mechanisms are involved.
Area of Science:
- Cell biology
- Molecular oncology
- Biochemistry
Background:
- Oncogene-transformed cells often exhibit altered morphology and reduced cell surface fibronectin.
- Glucocorticoids can revert the morphology of transformed human fibroblasts, correlating with increased fibronectin deposition.
Purpose of the Study:
- To investigate the differential effects of glucocorticoids on the morphology of various oncogene-transformed NIH3T3 mouse fibroblast cell lines.
- To determine if fibronectin expression is involved in the glucocorticoid-induced morphological changes in these cells.
Main Methods:
- Treatment of NIH3T3 cells transformed with neu, ras, src, sis, and abl oncogenes with glucocorticoids.
- Assessment of cellular morphology changes.
- Quantification of oncogene mRNA and protein expression.
- Measurement of cell surface fibronectin levels.
Main Results:
- Glucocorticoids induced a more normal morphology in neu-, ras-, src-, and sis-transformed NIH3T3 cells, but not in abl-transformed cells.
- The morphological changes were independent of alterations in oncogene expression.
- Unlike transformed human fibroblasts, most oncogene-transformed mouse cells (except abl) showed normal fibronectin levels, and glucocorticoid treatment did not increase fibronectin deposition despite morphological normalization.
Conclusions:
- Glucocorticoid-induced morphological reversion in oncogene-transformed NIH3T3 cells is oncogene-specific.
- The mechanism underlying this glucocorticoid effect in mouse cells does not involve increased fibronectin expression, indicating alternative pathways are responsible for the phenotypic changes.