Effect of adenosine 3',5'-cyclic monophosphate (cAMP) on human non-tumorigenic and tumorigenic parotid acinar cells in culture.
Adenosine 3',5'-cyclic monophosphate (cAMP) regulates growth and/or differentiation of some tumor cells in culture. The effects of cAMP on human parotid acinar cells have never been studied. Results showed that 2HPC8 (non-tumorigenic cells derived from human pleomorphic parotid adenoma) were more sensitive to dibutyryl cAMP, an analog of cAMP, and RO20-1724, an inhibitor of cyclic nucleotide phosphodiesterase, than 2HP1G cells (derived from spontaneous transformation of 2HPC8 cells), suggesting that human parotid adenoma cells maintain a higher degree of cAMP-responsiveness than parotid carcinoma cells. Prostaglandin E1 (PGE1), a stimulator of adenylate cyclase, which increased cAMP levels in 2HPC8 cells, but not in 2HP1G cells, caused a greater degree of growth inhibition in 2HP1G cells than in 2HPC8 cells, suggesting that this effect of PGE1 on tumorigenic cells is not related to cAMP. In the normal parotid and parotid adenoma cell cultures, about 5-10% of cells were small and round, whereas in tumorigenic cell cultures, all cells were small and round. Some indirect evidence suggests that these round cells may be the primary target for transformation. These tumor cells formed cytoplasmic processes of variable length after treatment with cAMP stimulating agents and prostaglandin E1.
Krause
G
G
Center for Vitamins and Cancer Research, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Kumar
R
R
Meyers
A
A
Prasad
K N
KN
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D008949:Adenoma, Pleomorphic / Q000378:metabolism / Q000473:pathology*; D000527:Alprostadil / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D006801:Humans; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects*; D010307:Parotid Neoplasms / Q000378:metabolism / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D018078:Receptors, Prostaglandin E; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000527:Alprostadil