The expression of alpha, beta and gamma retinoic acid receptors (RAR) was analyzed by reverse transcription polymerase chain reaction (RT/PCR) in several neuroblastoma derived cell lines before and after exposure to 10 nM retinoic acid. Each cell line shows a different receptor pattern: RAR alpha mRNA is ubiquitously present, whereas RAR beta and RAR gamma mRNAs are not always expressed. After retinoic acid treatment at physiological concentration, the majority of cell lines shows expression of all three receptors but two are resistant to the retinoid in expressing RAR beta mRNA. These data suggest that each NB cell line follows a particular retinoic acid-dependent differentiation route, at least with regard to the expression of RAR alpha, beta and gamma receptors. In an attempt to develop a biochemical classification of neuroblastomas, which could also be useful in the prognosis of the disease, we have screened biopsies belonging to patients in different clinical stages for the distribution of RAR receptors. The results show that the pattern of RAR alpha, beta and gamma mRNAs expression is rather variable in fresh tumors even if they are classified at the same stage. This may account for heterogeneous tumor cell composition which has in turn its own complement of RA receptors.

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