Expression of insulin-like growth factor (IGF)-II and IGF-I receptor during proliferation and differentiation of CaCo-2 human colon carcinoma cells.
We have studied the expression of insulin-like growth factor type II (IGF-II) and its autocrine role during the proliferation and differentiation of the CaCo-2 colon carcinoma cell line. IGF-II RNA levels were high in proliferating cells and decreased by more than 10-fold when cells ceased to proliferate and differentiated. Immunoreactive IGF-II protein was high in the conditioned media of proliferating cells and decreased 20-fold in the media of differentiated cells. Reduced IGF-II expression was associated with a decrease in IGF-I receptor number that was high in proliferating cells (approximately 80,000 binding sites/cell) and reduced by 4-fold in differentiated cells. Exogenously added IGF-II was able to stimulate proliferation of serum-deprived cells in a dose-dependent fashion. IGF-II acted through the IGF-I receptor, since both basal and IGF-II-stimulated cell proliferation was inhibited by the monoclonal antibody alpha-IR3, which blocks the binding sites of the IGF-I receptor. The inhibition of CaCo-2 basal cell growth by the alpha-IR3 antibody suggests that IGF-II may act as an autocrine growth factor for these cells.
Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano,Facoltà de Medicina e Chirurgia, Università di Napoli Federico II, Italy.
R
R
Zarrilli
S
S
Pignata
M
M
Romano
A
A
Gravina
S
S
Casola
C B
CB
Bruni
A M
AM
Acquaviva
D000911:Antibodies, Monoclonal; D001481:Basal Metabolism; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008969:Molecular Sequence Data; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1