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(Received for publication, January 31, 1996, and in revised form, June 28, 1996)
From the Although adrenomedullin (AM) previously has been
identified in human tumors, its role has remained elusive. Analysis by
reverse transcriptase-polymerase chain reaction (RT-PCR) revealed AM
mRNA in 18 of 20 human normal tissues representing major organs,
and 55 of 58 (95%) malignant cell lines. Western blot and high
performance liquid chromatography analysis showed immunoreactive AM
species of 18, 14, and 6 kDa that are consistent with the precursor,
intermediate product, and active peptide, respectively.
Immunohistochemistry and in situ RT-PCR performed on
paraffin-embedded tumor cell lines of various tissue origins exhibited
AM cytoplasmic staining. Neutralizing monoclonal antibody to AM
inhibits tumor cell growth in a concentration-dependent
manner, an effect that was reversed with the addition of exogenous AM.
Responding tumor cells were shown to have approximately 50,000 AM
receptors per cell by Scatchard analysis with 125I-AM and
expressed AM receptor mRNA by RT-PCR. Our data showed 36 of 48 (75%) tumor cell lines expressed AM receptor mRNA by RT-PCR
assessment, all of them also expressed AM. In the presence of AM, cAMP
levels were shown to increase in tumor cells. Our collective data
demonstrate that AM and AM receptor are expressed in numerous human
cancer cell lines of diverse origin and constitute a potential
autocrine growth mechanism that could drive neoplastic
proliferation.
Volume 271, Number 38,
Issue of September 20, 1996
pp. 23345-23351
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
ITS POTENTIAL ROLE AS AN AUTOCRINE GROWTH FACTOR
,
,
,
,
and
Biomarkers and Prevention Research Branch,
Division of Clinical Sciences, National Cancer Institute, Rockville,
Maryland 20850, the ¶ Pediatric Branch, Division of Cancer
Treatment, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland 20892, and the 
U. S. Department of
Agriculture, Agricultural Research Service,
Beltsville, Maryland 20705
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