Effect of glucocorticoids on oncogene transformed NIH3T3 cells

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.