This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schroder, E. W. Articles by Black, P. H. Search for Related Content PubMed PubMed Citation Articles by Schroder, E. W. Articles by Black, P. H.

Effects of Retinoic Acid on Plasminogen Activator and Mitogenic Responses of Cultured Mouse Cells¹

Department of Medicine, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Treatment of simian virus 40-transformed 3T3 cells with 1 µM ß-all-trans-retinoic acid (RA) resulted in a 5- to 6-fold enhancement of plasminogen activator (PA) release. Intracellular PA levels rose to twice control levels. Confluent 3T3 cells were less responsive to RA. In 6 of 10 experiments, no increase in 3T3 cell PA levels was noted, although up to a 2.5-fold enhancement of PA elaboration has been observed in some experiments at a dose of 10 µM RA. Simultaneous treatments of 3T3 cells with 10 µM RA and 2.1 to 9.3 mM Ca²⁺, 5 to 40 ng phorbol myristate acetate per ml, or 150 to 600 ng Fraction I from lactalbumin hydrolysate (FI) protein per ml indicated that RA potentiated the PA stimulatory activities of these agents. Extracellular PA levels of RA-treated cells increased by 4 to 10 times the amount of increase observed for Ca²⁺, PMA, or FI alone. A potentiating activity of RA was also evident when quiescent 3T3 cells were pretreated with 10 µM RA and then stimulated to synthesize DNA with Ca²⁺, PMA, or FI. For RA-pretreated cells, an increased percentage of nuclei was labeled with [³H]thymidine (24 hr) in response to doses of the three mitogens which were ineffective without RA pretreatment (2.4 mM Ca²⁺, 5 ng PMA per ml, or 150 ng FI protein per ml). Additional experiments have indicated that, like platelet extracts, RA renders quiescent 3T3 cells competent to synthesize DNA in response to the progression factors of human plasma as defined by Pledger et al. (Proc. Natl. Acad. Sci. U. S. A., 74: 4481–4485, 1977). Pretreatment of quiescent 3T3 cells for 6 hr with 10 µM RA resulted in a greater than 4-fold increase in the percentage of cells which incorporated [³H]thymidine in response to a 36-hr treatment with 10% human plasma, as compared to cells treated with human plasma alone. Thus, under certain conditions, RA may have cell-activating properties, and caution should be exercised with regard to its suggested use as an antitumor agent.

¹ This work was supported by Grant CA-10126 from the NIH.

² Recipient of National Research Service Award CA-05975 from the National Cancer Institute.

³ Recipient of a Cancer Research Scholar Award from the American Cancer Society, Massachusetts Division.

⁴ Present address, Department of Microbiology, Boston University School of Medicine, Boston, Mass. 02118.

Received 12/11/79. Accepted 5/ 5/80.