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KMID : 0390119940340020289
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Journal of Pusan Medical College
1994 Volume.34 No. 2 p.289 ~ p.304
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Effects of All-Trans-Retinoic Acid on Immortalized Human Epidermal Keratinocyte, RHEK-1
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Abstract
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The aim of this study was to determine the effects of all-trans-retinoic acid on cell proliferation and cell adhesion in immortalized human epidermal keratinocytes. As a model, RHEK-1 cells and its oncogene transformed sublines, RHEK/ras and
RHEK/fos,
were used to assess the effects. The effects of hydrocortisone whichh was the most potent and widely used antiinflammatory agents for various skin disorders were examined aslo.
All-trans-retinoic acid and hydrocortisone at the concentration used in this experiment did not alter morphology of RHEK-1 cells. Cell count to assess the ability of cell growth, microculture tetrazolium assay for metabolic activity and
[3H]thymidine
incorporation for DNA synthesis were performed. All-trans-retinoic acid exhibited stimulatory effects on RHEK-1 cell proliferation at 0.1μM~1.0μM and exhibited cytotoxicity above 10μM, but not in RHEK/fos and RHEK/ras cells.
Cell Attachment test and cell detachment test showed that hydrocortisone decreased cell adhesiveness and this effect was reversed by addition of all-trans-retinoic acid. The effect of hydrocortisone on cell adhesion in RHEK-1 cells was different
from
the effect in RHEK/fos cells. Northern blot analysis was done to access the molecular basis of the effect of all-trans-retinoic acid and hydrocortisone on cell adhesion. The fibronectin mRNA expression in RHEK-1 cells was less than that in
RHEK/fos
cells. This result suggest that the difference o cell adhesiveness might be resulted from the extent of expression in fibronectin mRNA. Hydrocortisone increased the expression of fibronectin mRNA in rHEK-1 cells, but decreased the expression in
RHEK/for
cells. All-trans-retinoic acid increased the expression of fibronectin mRNA.
In summary all-trans-retinoic acid increased cell proliferation and adhesiveness in RHEK-1 cells. However, in transformants, RHEK/for and RHEK/ras cells, all-trans-retinoic acid had no effect on cell proliferation. These results suggest tha the
effects
of all-trans-retinoic acid on cell proliferation and adhesiveness were modulated by the expression of c-fos and Ha-ras oncogenes.
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KEYWORD
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