Alpha-amidation of peptide hormones in lung cancer.
Small-cell lung cancer (SCLC), the most common neuroendocrine tumor in humans, provides an excellent model system for analyzing the role of growth factors in lung cancer. SCLCs secrete a wide range of peptide hormones, including some that stimulate tumor cell growth, such as gastrin-releasing peptide and insulin-like growth factor I. Many of these peptides are synthesized as prohormones that acquire biological activity only after specific post-translational modifications. Here, we review our current understanding of the biological role of neuroendocrine peptides in lung carcinogenesis and consider how a mechanistic knowledge of one particular modification, carboxy-terminal alpha-amidation, may permit identification of novel growth factors for lung cancer cells. We also describe potential applications of this knowledge as a basis for prevention-oriented approaches to the disease.
Quinn
K A
KA
Biomarkers and Prevention Research Branch Control, National Naval Medical Center, Bethesda, Maryland 20889.
Treston
A M
AM
Scott
F M
FM
Kasprzyk
P G
PG
Avis
I
I
Siegfried
J M
JM
Mulshine
J L
JL
Cuttitta
F
F
D000577:Amides / Q000378:metabolism; D019760:Amidine-Lyases; D000595:Amino Acid Sequence; D000818:Animals; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008190:Lyases / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D000577:Amides; D006133:Growth Substances; D006728:Hormones; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010455:Peptides; D011498:Protein Precursors; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D008190:Lyases; D019760:Amidine-Lyases; C068521:peptidylamidoglycolate lyase; D005998:Glycine