gastrin-releasing-peptide and Chromosome-Deletion

Small cell lung cancer (SCLC) is histologically simple and looks undifferentiated, but possesses cytoplasmic dense-cored granules resembling neuroendocrine granules, and frequently produces amine and peptide hormones, occasionally presenting related symptoms. Among these bioactive substances, gastrin releasing peptide (GRP) is most important, which is known as autocrine growth factor and one of the useful monitoring markers for SCLC together with neuron-specific enolase. Aromatic L-amino acid decarboxylase is another important enzyme in SCLC. Abnormality of myc family oncogenes is occasionally noted in SCLC, which appears related to proliferative activity of the tumor rather than development. Deletion of chromosomes 3p, 13q and 17p is noted in almost every SCLC, where antioncogene is suspected to be present, and inactivation of antioncogene may play an important role in development of SCLC. Nucleolar size is the important parameter for proliferative potential of SCLC. The larger the nucleoli, the faster is the growth of SCLC. Phenotypes of SCLC in vitro may be altered by change of microenvironment, although it may be due to the selective growth of a certain clone. SCLC and nervous tissue specific membrane antigen is named cluster 1 SCLC antigen, the monoclonal antibody to which will be utilized for immunohistological diagnosis, imaging and treatment of SCLC. Accumulation of basic knowledge is now leading to reconsideration of histological subtyping of SCLC.

Topics: Antibodies, Monoclonal; Aromatic-L-Amino-Acid Decarboxylases; Carcinoma, Small Cell; Cell Division; Cell Nucleolus; Chromosome Deletion; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 3; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Oncogenes; Peptide Biosynthesis

Topics: Bombesin; Chromosome Deletion; DNA, Neoplasm; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Neoplasms, Multiple Primary; Oncogenes; Peptides; Suppression, Genetic

The ability to establish long-term cell lines of small-cell lung cancer (SCLC) has provided an in vitro model for the disease. We report on the characterization of 10 new human SCLC cell lines established from 34 cytopathologically positive specimens. Based on morphologic and biochemical characterization, growth properties, and expression of MYC and neuroendocrine properties, eight cell lines were categorized as "classic" and two cell lines as "variant". Cytogenetic examination revealed loss of all or part of 3p in all nine SCLC cell lines analyzed. The smallest deletion in common was found at 3p21-3p25. Restriction fragment length polymorphism (RFLP) analyses with probes for 3p were performed for correlation with karyotypic data and supported the cytogenetic findings. In 21 SCLC specimens (cell lines and tumor tissue) with normal DNA, used for comparison, we observed loss of heterozygosity at RAF1 (3p25) in ten of ten informative pairs by using two RFLPs from the RAF1 locus. In addition, loss of heterozygosity was noted in nine of 10 pairs examined with DNF15S2 (3p21) and four of four with D3S3 (3p14). Analysis of cell lines and tumor specimens that lacked paired normal tissue showed a homozygous pattern with the RAF1 probes in all 18 cases. Northern blots revealed significant expression of RAF1 in all cell lines tested. The transcript size was normal. The cytogenetic and RFLP data suggest that the RAF1 locus at 3p25 is involved in the chromosomal deletion of SCLC.

Topics: Blotting, Northern; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Chromosome Deletion; Chromosomes, Human, Pair 3; DNA Mutational Analysis; DNA, Neoplasm; Gastrin-Releasing Peptide; Genes, myc; Heterozygote; Humans; Lung Neoplasms; Neoplasm Proteins; Peptides; Polymorphism, Restriction Fragment Length; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-raf; Proto-Oncogenes; Tumor Cells, Cultured