MOLECULAR CHARACTERIZATION OF THE HUMAN DELTA-OPIOID RECEPTOR IN LUNG-CANCER

A variety of neuropeptide receptors have been detected in human lung c ancer. They are thought to play a role in autocrine/paracrine regulati on of cell growth, and may be clinically useful as diagnostic, prognos tic or therapeutic targets. The current study characterizes the molecu lar structure of the delta opioid receptor and its gene expression lev el in lung cancer cell lines relative to normal human lung using a sen sitive RT-PCR approach. The goals of this investigation were a) to def ine the correlation between receptor binding and gene expression in lu ng cancer cell lines, and b) to determine the cDNA sequence integrity of this receptor in comparison to the receptor recently found in human brain. Five small cell lung cancer (SCLC) cell lines revealed size-ma tched RT-PCR products which strongly hybridized to the human brain del ta opioid receptor probe. One of three non-small cell lung cancel (NSC LC) cell lines (NCI-H23), known to be negative by binding analysis, de monstrated low level expression. No gene expression was found in norma l human lung. RT-PCR products fr om two SCLC cell lines (SCLC-22H and 16HC) as well as the low level expressing NSCLC cell line (NCI-23) wer e subjected to bidirectional DNA sequence analysis and the receptor en ds were resolved using a 3'-end RACE and 5'-end gene-specific approach . The isolated cDNA sequences proved to be identical to the published human brain delta opioid receptor sequence. These data show that lung cancels with neuroendocrine features express human brain delta opioid receptors in contrast to normal lung, and that the delta opioid recept or mRNA in lung cancer is not mutated. This unique feature of lung can cer may be exploitable for diagnostic, prognostic, and therapeutic str ategies.