TY - JOUR
T1 - Insulin-like growth factor binding protein-6 inhibits the growth of human bronchial epithelial cells and increases in abundance with all-trans-retinoic acid treatment
AU - Sueoka, N.
AU - Lee, H. Y.
AU - Walsh, G. L.
AU - Fang, B.
AU - Ji, L.
AU - Roth, J. A.
AU - LaPushin, R.
AU - Hong, W. K.
AU - Cohen, P.
AU - Kurie, J. M.
PY - 2000
Y1 - 2000
N2 - Retinoids are potent inhibitors of human bronchial epithelial (HBE) cell growth. Retinoids initiate signaling through activation of nuclear receptors, but the signal transduction pathways that mediate growth inhibition have not been defined. In this study, we investigated the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 as a potential mediator of retinoid actions. IGFBP-6 is a secreted glycoprotein that inhibits the bioavailability of IGFs, which are potent mitogens of HBE cells. IGFBP-6 was detected by immunohistochemical staining in the basal epithelial layer of human bronchial organ cultures, and all-trans-retinoic acid (t-RA) treatment increased the intensity of IGFBP-6 immunostaining. In primary cultures of HBE cells treated with t-RA, IGFBP-6 messenger RNA and protein levels increased within 6 and 24 h, respectively, and IGFBP-6 was detected in the conditioned media at 48 h. The effect of IGFBP-6 on HBE cell growth was investigated with a recombinant adenoviral vector, Ad5CMV-BP6, which expresses IGFBP-6 under the control of a cytomegalovirus promoter. IGFBP-6 overexpression induced a proliferative arrest of HBE cells with no evidence of apoptosis. These findings provide the first evidence that IGFBP-6 is expressed in the bronchial epithelium and that IGFBP-6 may contribute to the biologic effects of retinoids on HBE cells.
AB - Retinoids are potent inhibitors of human bronchial epithelial (HBE) cell growth. Retinoids initiate signaling through activation of nuclear receptors, but the signal transduction pathways that mediate growth inhibition have not been defined. In this study, we investigated the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 as a potential mediator of retinoid actions. IGFBP-6 is a secreted glycoprotein that inhibits the bioavailability of IGFs, which are potent mitogens of HBE cells. IGFBP-6 was detected by immunohistochemical staining in the basal epithelial layer of human bronchial organ cultures, and all-trans-retinoic acid (t-RA) treatment increased the intensity of IGFBP-6 immunostaining. In primary cultures of HBE cells treated with t-RA, IGFBP-6 messenger RNA and protein levels increased within 6 and 24 h, respectively, and IGFBP-6 was detected in the conditioned media at 48 h. The effect of IGFBP-6 on HBE cell growth was investigated with a recombinant adenoviral vector, Ad5CMV-BP6, which expresses IGFBP-6 under the control of a cytomegalovirus promoter. IGFBP-6 overexpression induced a proliferative arrest of HBE cells with no evidence of apoptosis. These findings provide the first evidence that IGFBP-6 is expressed in the bronchial epithelium and that IGFBP-6 may contribute to the biologic effects of retinoids on HBE cells.
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U2 - 10.1165/ajrcmb.23.3.4013
DO - 10.1165/ajrcmb.23.3.4013
M3 - Article
C2 - 10970819
AN - SCOPUS:0033831656
SN - 1044-1549
VL - 23
SP - 297
EP - 303
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 3
ER -