title: Investigation of the genes for RET and its ligand complex, GDNF/GFR alpha-I, in small cell lung carcinoma.
abstract: RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors of these cell types. RET activation may be mediated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha-1 (GFR alpha-1). Activating RET mutations are found in the inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of the related sporadic tumors, medullary thyroid carcinoma and pheochromocytoma, both being derived from neuroendocrine tissues. In one small study, mutations were identified in another tumor with neuroendocrine features, small cell lung carcinoma (SCLC). To determine whether RET mutations contribute to the pathogenesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutations were identified in RET exons 10, 11, and 13-16, regions previously implicated in SCLC or other neuroendocrine tumors. We further examined the expression pattern of RET and the genes encoding the components of its ligand complex GDNF and GFR alpha-1, in 21 SCLC lines by using RT-PCR. Although we found no consistent pattern of expression for these three genes, RET was expressed in 57% of SCLC lines. Thus, although RET mutations appear unlikely to be an important step in the tumorigenesis of SCLC, the frequent expression of this gene suggests that RET may have a mitogenic role in a subset of SCLC cell lines.
authors.affiliation: Department of Pathology, Queen's University, Kingston, Ontario, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: T
authors.initials: T
authors.lastname: Timmer
authors.forename: S M
authors.initials: SM
authors.lastname: Ivanchuk
authors.forename: B G
authors.initials: BG
authors.lastname: Campling
authors.forename: L C
authors.initials: LC
authors.lastname: Young
authors.forename: P H
authors.initials: PH
authors.lastname: Rabbitts
authors.forename: V
authors.initials: V
authors.lastname: Sundaresan
authors.forename: R M
authors.initials: RM
authors.lastname: Hofstra
authors.forename: C
authors.initials: C
authors.lastname: Eng
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000302:isolation & purification; D029721:Drosophila Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012334:RNA, Neoplasm / Q000302:isolation & purification; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C495039:GDNF protein, human; C494987:GFRA1 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila