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)
Department of Biochemistry, Boston University School of Medicine, MA 02118.
R M
RM
Niles
B P
BP
Loewy
K
K
Brown
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D015342:DNA Probes; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D016283:Proto-Oncogene Proteins p21(ras); D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis / Q000235:genetics; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D014212:Tretinoin; D012313:RNA; D016283:Proto-Oncogene Proteins p21(ras)