Dietary calcium and growth modulation of human colon cancer cells: role of the extracellular calcium-sensing receptor.
Cancer Detect Prev
; 24(2): 127-36, 2000.
Article
em En
| MEDLINE
| ID: mdl-10917132
ABSTRACT
Using the human colon adenocarcinoma-derived cell line Caco-2, we investigated the possible role of the Ca2+-sensing receptor (CaR) in mediating effects of extracellular Ca2+ on cellular proliferation. Caco-2 cells respond to low ambient [Ca2+]o by activation of the protein kinase C-signaling pathway, leading to upregulation of c-myc mRNA expression and thereby, finally, to alleviation from the G1/S phase control of the cell cycle. This proliferative response can be reverted by activation of the CaR either through raising [Ca2+]o or, respectively, by using the CaR agonist Gd3+ as a substitute for Ca2+. The inhibitory effect of [Ca2+]o on cell replication exhibits saturation kinetics (IC50 = 0.045 mM), indicating the existence of a highly sensitive CaR operating at low ambient [Ca2+]o. Specific immunostaining revealed the presence of CaR-positive cells in the crypt epithelium of normal human colonic mucosa as well as in glandular (i.e., differentiated structures) of carcinomatous lesions. This could provide a rationale for use of calcium supplements for intervention in early phases of colon tumorigenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Cálcio da Dieta
/
Adenocarcinoma
/
Colo
/
Neoplasias do Colo
/
Células CACO-2
Limite:
Humans
Idioma:
En
Revista:
Cancer Detect Prev
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Áustria