Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography.
Using in situ hybridization techniques with selective oligoprobes, the gene expression of sst1, sst2, sst3 and sst5 was studied in a series of 32 human pituitary adenomas, 28 breast tumors and 21 endocrine gastroentero-pancreatic tumors, shown to express somatostatin receptors to variable extents. In most of these tumors the sst2 receptor subtype was abundantly expressed, even though a significant number of pituitary adenomas, breast and gastroentero-pancreatic tumors expressed sst1 and/or sst3 as well. A very high incidence of the sst5 subtype was found in growth hormone-producing pituitary adenomas and, to a lesser extent, in inactive pituitary adenomas, whereas breast tumors seldom expressed sst5; gastroentero-pancreatic tumors showed all possible combinations of sst expression, with, however, a predominance of sst2 and sst1. Overall, the presence of sst2 mRNA and/or sst5 mRNA generally correlated with the presence of octreotide binding sites. A lack of octreotide binding sites corresponded with a lack of sst2 mRNA. Several tumors exhibiting a low number of octreotide binding sites had no measurable sst2 mRNA, despite abundance of beta-actin mRNA, suggesting in these cases a very low abundance of sst mRNAs or a too low sensitivity of the in situ hybridization methodology. In all other cases, the method allowed precise localization of the respective mRNAs on the tumor tissue, notably in breast tumors with non-homogeneous receptor distribution. Tumors without measurable amounts of somatostatin receptors had no detectable sst mRNA. Our results indicate a highly variable abundance of the various sst mRNAs in individual somatostatin receptor-containing tumors.
Schaer
J C
JC
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland.
Waser
B
B
Mengod
G
G
Reubi
J C
JC
D001345:Autoradiography; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism*
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5