Detection of somatostatin receptor subtype 2 (SSTR2) in established tumors and tumor cell lines: evidence for SSTR2 heterogeneity.
The somatostatin receptor subtype 2 (SSTR2) was detected in a wide range of human and rat tumors using in vitro receptor binding ([125I]MK-678), receptor gene expression analysis, and immunoblotting techniques. The highest receptor concentrations were observed in the rat AR42J pancreatic and human small cell lung cancer (SCLC) cell lines, NCI-H69 and NCI-H345, with much lower levels detected in breast, prostate, melanoma, and hepatic tumors. Several human pancreas tumors were devoid of SSTR2. For all tumors showing detectable [125I]MK-678 binding, SSTR2 receptor mRNA was expressed. Furthermore, a mRNA transcript corresponding to a truncated isoform of SSTR2 was detected at low levels in the human SCLC NCI-H69 cell line, and likely represents a human homologue of rodent SSTR2B. Immunoblotting analysis using the SSTR2-specific antibody, 2e3, detected multiple immunoreactive protein species, including a predominant 150-kDa molecule, which could be blocked by the SSTR2-derived 2e3 peptide. Somatostatin (SRIF) peptides with high SSTR2 affinity and antiproliferative properties were potent inhibitors of [125I]MK-678 binding to several tumor types, suggesting that they may exert antitumor effects via the SSTR2 receptor.
Taylor
J E
JE
Biomeasure Inc., Milford, MA 01757-3650.
Theveniau
M A
MA
Bashirzadeh
R
R
Reisine
T
T
Eden
P A
PA
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D017481:Receptors, Somatostatin