Neuroblastoma Cell Line Phenotypes after Induction of Differentiation in a Human Activation of Distinct Molecular and Cellular In Vitro

In this report we provide evidence for the activation of distinct dif ferentiation pathways during treatment of the neuroblastoma cell line SMS-KCNR with 1 mm dibutyryl cyclic AMP (dbcAMP) and/or 5 MM retinole acid (RA). Our results show that the adrenal gland specific gene pG2 is induced only during dbcAMP treatment, while RA induces a neuronal phenotype and expression of all neural related genes while decreasing the expression of many chromaffin related genes. Further more dbcAMP does not affect the DNA content distribution of SMSKCNR cells |G,=61.8 ±4.1% (SD); S = 20.3 ±6.3%; G2-M = 18 ± 5.4%] despite morphological and molecular signs of cellular differenti ation. Conversely, RA arrests cell growth causing a decrease in cells in the growth fraction (S + G2 + M = 15.6 ±6.1%) and an increase in cells in (., (c;, 84.3 ±5%). Using cyclic AMP and RA in combination, we found that RA inhibited expression of adrenal gland specific gene pG2 and induced a neuronal phenotype. Since dbcAMP does not cause a significant GI block in SMS-KCNR cells we propose that this agent may be able to induce SMS-KCNR only to an intermediate stage of chromaffin differentiation in which cells retain their proliferative po tential.