Biology of small cell lung cancer.
The bombesin-like peptides can function as autocrine growth factors in lung cancer and candidate tumor suppressor genes on chromosomes 3 and 9 play important roles in lung cancer. Bombesin-like peptides can function as mitogens for normal bronchial epithelial cells and lung cancer cell lines. The monoclonal antibody directed against gastrin releasing peptide and bombesin, 2A11, can inhibit the growth of small cell lung cancer in vitro and in vivo and intravenous administration has induced a clinical remission in a patient with relapsed small cell lung cancer. The loss of a portion of one of the two short arms of chromosome 3 (3p) is identified in nearly 100% of tumor cell lines and tumors from patients with small cell lung cancer. Introduction of chromosome 3 into tumor cell lines suppresses their tumorigenicity in athymic nude mice, one of the characteristics of the cancer phenotype. Both copies of the candidate tumor suppressor gene on chromosome 9, CDKN2, are deleted in approximately one-fourth of lung cancer cell lines examined and the protein product of CDKN2, p16 is undetectable in one-third of the lung cancer cell lines studied. The CDKN2 gene is inactivated more commonly in non-small cell lung cancer than small cell lung cancer while the retinoblastoma gene is inactivated more commonly in small cell lung cancer than non-small cell lung cancer. It appears that a single defect in this cell cycle pathway is necessary for unregulated growth in lung cancer and current evidence suggests these defects differ between small cell and non-small cell lung cancer.
Johnson
B E
BE
Lung Cancer Biology Section, National Cancer Institute -- Navy Medical Oncology Branch, Bethesda, MD 20889-5105, USA.
Kelley
M J
MJ
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins / Q000502:physiology; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens / Q000494:pharmacology; D012150:Polymorphism, Restriction Fragment Length; D014183:Transplantation, Heterologous
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D006133:Growth Substances; D008934:Mitogens; D001839:Bombesin