The effect of retinoic acid on growth and proto-oncogene expression in hamster tracheal epithelial cells

Retinoic acid (RA) has been shown to be required for the maintenance of epithelial differentiation. Vitamin A deficiency in hamsters induces the tracheal epithelial cells to undergo squamous metaplasia. Reversing the vitamin deficiency restores the tracheal epithelial cells to their normal morphology and function. Using a hamster tracheal epithelial (HTE) cell culture system which undergoes differentiation to predominantly secretory cells in vitro, we found that RA can convert flat, squamous-like cells to compact, cuboidal-like cells, and that it stimulated cell proliferation. The mitogenic response to RA was maximal at 10(-7) M and required at least 48 h of treatment to observe the effect. RNA levels of growth-related genes during the growth and differentiation phases of primary HTE cultures were examined by Northern analysis. RA maintained a high level of c-myc RNA expression in preconfluent cultures, whereas untreated cells had low amounts of c-myc RNA. Expression of RNA for the replication-dependent histone 3.2 followed a similar pattern, i.e., its level was high in retinoid-treated versus control preconfluent cultures. In confluent (fully differentiated) HTE cell cultures, both retinoid-treated and control cells had low RNA levels of c-myc and histone 3.2. c-fos RNA levels were undetectable in either control or treated cells at any stage during primary culture. The RNA level of c-Ha-ras was very low in both control and treated cultures and did not vary with the state of growth or differentiation, except that when RA-treated cultures reached confluence, no c-Ha-ras RNA was detected.(ABSTRACT TRUNCATED AT 250 WORDS)