Cyclic AMP-dependent secretion of Ca 19-9 by LS174T human colon carcinoma cells.
Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in culture medium of a human colon cancer cell (LS174T) inhibits cellular growth and stimulates Ca 19-9 expression. The raise in cAMP level was produced by dibutyryl cyclic AMP (DBcAMP) or by forskolin an agent acting at the level of cAMP generation. Both these agents in a range of concentration between 10(-3)-10(-5) M have an inhibitory effect on the growth which is dose and time dependent. The inhibition was reversible as demonstrated by complete restoration of cell growth soon after the withdrawal of the substances from the culture medium. When cAMP levels in culture medium was raised, an increase in Ca 19-9 expression was observed and it appears that cyclic nucleotides have at least two effects: the first to cause rapid release of already synthesized Ca 19-9 and second to stimulate new antigen synthesis. The findings of the present study demonstrated that LS174T cells are unable to proliferate upon sustained accumulation of intracellular cyclic AMP suggesting the use of strategies able to increase cAMP levels for therapy of colon cancer. Furthermore, the finding that cAMP may also be a regulator of Ca 19-9 synthesis and release indicates the utility of cell line LS174T as a model for studies on the mechanism of synthesis and secretion of specific tumoral markers in colon cancer.
Macchia
Vincenzo
V
Dipartimento di Biologia e Patologia Cellulare e Molecolare <L. Califano>, Universita di Napoli <Federico II>, I-80131 Napoli, Italy. macchia@unina.it
Gargiulo
Maria
M
Terracciano
Daniela
D
Di Carlo
Angelina
A
Mariano
Angela
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D018395:CA-19-9 Antigen / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D018395:CA-19-9 Antigen; D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine