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Tumor necrosis factor induces neuroendocrine differentiation in small cell lung cancer cell lines. 1998

K J Haley, and K Patidar, and F Zhang, and R L Emanuel, and M E Sunday
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

We studied tumor necrosis factor (TNF)-alpha as a candidate cytokine to promote neuroendocrine cell differentiation in a nitrosamine-hyperoxia hamster lung injury model. Differential screening identified expression of the genes modulated by TNF-alpha preceding neuroendocrine cell differentiation. Undifferentiated small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H526 were treated with TNF-alpha for up to 2 wk. Both cell lines demonstrated rapid induction of gastrin-releasing peptide (GRP) mRNA; H82 cells also expressed aromatic-L-amino acid decarboxylase mRNA within 5 min after TNF-alpha was added. Nuclear translocation of nuclear factor-kappaB immunostaining occurred with TNF-alpha treatment, suggesting nuclear factor-kappaB involvement in the induction of GRP and/or aromatic-L-amino acid decarboxylase gene expression. We also demonstrated dense core neurosecretory granules and immunostaining for proGRP and neural cell adhesion molecule in H82 cells after 7-14 days of TNF-alpha treatment. We conclude that TNF-alpha can induce phenotypic features of neuroendocrine cell differentiation in SCLC cell lines. Similar effects of TNF-alpha in vivo may contribute to the neuroendocrine cell differentiation/hyperplasia associated with many chronic inflammatory pulmonary diseases.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D009490 Neurosecretory Systems A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ. Neuroendocrine System,Neuroendocrine Systems,Neurosecretory System,System, Neuroendocrine,System, Neurosecretory,Systems, Neuroendocrine,Systems, Neurosecretory
D009602 Nitrosamines A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. Nitrosamine
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001142 Aromatic-L-Amino-Acid Decarboxylases An enzyme group with broad specificity. The enzymes decarboxylate a range of aromatic amino acids including dihydroxyphenylalanine (DOPA DECARBOXYLASE); TRYPTOPHAN; and HYDROXYTRYPTOPHAN. Amino Acid Decarboxylases, Aromatic,Aromatic Amino Acid Decarboxylase,Aromatic Amino Acid Decarboxylases,5-HTPase,5-Hydroxytryptophan Decarboxylase,Aromatic-L-Amino-Acid Decarboxylase,Hydroxytryptophan Decarboxylase,Tryptophan Decarboxylase,5 HTPase,5 Hydroxytryptophan Decarboxylase,Aromatic L Amino Acid Decarboxylase,Aromatic L Amino Acid Decarboxylases,Decarboxylase, 5-Hydroxytryptophan,Decarboxylase, Aromatic-L-Amino-Acid,Decarboxylase, Hydroxytryptophan,Decarboxylase, Tryptophan,Decarboxylases, Aromatic-L-Amino-Acid

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