DISTRIBUTION OF RETINOIC ACID RECEPTOR-ALPHA, RECEPTOR-BETA AND RECEPTOR-GAMMA MESSENGER-RNAS IN NEUROBLASTOMA-DERIVED CELL-LINES AND IN FRESH TUMORS

The expression of alpha, beta and gamma retinoic acid receptors (RAR) was analyzed by reverse transcription polymerase chain reaction (RT/PC R) in several neuroblastoma derived cell lines before and after exposu re to 10 nM retinoic acid. Each cell line shows a different receptor p attern: RAR alpha mRNA is ubiquitously present, whereas RAR beta and R AR gamma mRNAs are not always expressed. After retinoic acid treatment at physiological concentration, the majority of cell lines shows expr ession of all three receptors but two are resistant to the retinoid in expressing RAR beta mRNA. These data suggest that each NB cell line f ollows a particular retinoic acid-dependent differentiation route, at least with regard to the expression of RAR alpha, beta and gamma recep tors. In an attempt to develop a biochemical classification of neurobl astomas, which could also be useful in the prognosis of the disease, w e have screened biopsies belonging to patients in different clinical s tages for the distribution of RAR receptors. The results show that the pattern of RAR alpha, beta and gamma mRNAs expression is rather varia ble in fresh tumors even if they are classified at the same stage. Thi s may account for heterogeneous tumor cell composition which has in tu rn its own complement of RA receptors.