TY - JOUR
T1 - Effects of transforming growth factor β (TGF-β) receptor on lung carcinogenesis
AU - Park, C.
AU - Kim, W. S.
AU - Choi, Y.
AU - Kim, H.
AU - Park, K.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Transforming growth factor β (TGF-β) type-II receptor mutations have been reported in several epithelial-type human malignancies. To elucidate the role of TGF-β RII in lung cancer progression, we prepared gene-modified clones of the human lung cancer cell line NCI-H23. NCI-H23, a human non-small-cell lung adenocarcinoma cell line which has a frameshift mutation in, and reduced expression of, the TGF-β type-II receptor (TGF-β RII), exhibits resistance to growth inhibition by TGF-β1 in vitro. Transfection of NCI-H23 with a retroviral vector expressing wild-type TGF-β RII restored the responsiveness of cells to exogenous TGF-β1 with reduced cell proliferation. Immunocytochemical analysis demonstrated nuclear translocation of Smad3 after TGF-β1 treatment in RII-restored NCI-H23 cells. Underphosphorylation of the retinoblastoma protein accompanying p21 up-regulation was observed after TGF-β1 treatment of NCI-H23-RII cells. Receptor restoration also changed the levels of VEGF mRNA induced by TGF-β1. However, impairment of TGF-β signalling did not alter microvessel formation in vivo in transplanted tumours. Instead, in vivo tumorigenesis experiments revealed a remarkable difference in the number and sizes of the tumours derived from NCI-H23-RII cells and dominant negative NCI-H23-dnRII cells (P<0.01). Collectively, these observations suggest that impairment of TGF-β signal transduction contributes significantly to tumour progression, mainly by cell proliferation rather than by modulation of angiogenesis in human NCI-H23 lung carcinoma cells.
AB - Transforming growth factor β (TGF-β) type-II receptor mutations have been reported in several epithelial-type human malignancies. To elucidate the role of TGF-β RII in lung cancer progression, we prepared gene-modified clones of the human lung cancer cell line NCI-H23. NCI-H23, a human non-small-cell lung adenocarcinoma cell line which has a frameshift mutation in, and reduced expression of, the TGF-β type-II receptor (TGF-β RII), exhibits resistance to growth inhibition by TGF-β1 in vitro. Transfection of NCI-H23 with a retroviral vector expressing wild-type TGF-β RII restored the responsiveness of cells to exogenous TGF-β1 with reduced cell proliferation. Immunocytochemical analysis demonstrated nuclear translocation of Smad3 after TGF-β1 treatment in RII-restored NCI-H23 cells. Underphosphorylation of the retinoblastoma protein accompanying p21 up-regulation was observed after TGF-β1 treatment of NCI-H23-RII cells. Receptor restoration also changed the levels of VEGF mRNA induced by TGF-β1. However, impairment of TGF-β signalling did not alter microvessel formation in vivo in transplanted tumours. Instead, in vivo tumorigenesis experiments revealed a remarkable difference in the number and sizes of the tumours derived from NCI-H23-RII cells and dominant negative NCI-H23-dnRII cells (P<0.01). Collectively, these observations suggest that impairment of TGF-β signal transduction contributes significantly to tumour progression, mainly by cell proliferation rather than by modulation of angiogenesis in human NCI-H23 lung carcinoma cells.
KW - Lung carcinogenesis
KW - Non-small-cell lung cancers
KW - Transforming growth factor β
UR - https://www.scopus.com/pages/publications/0036837999
U2 - 10.1016/S0169-5002(02)00182-4
DO - 10.1016/S0169-5002(02)00182-4
M3 - Article
C2 - 12399125
AN - SCOPUS:0036837999
SN - 0169-5002
VL - 38
SP - 143
EP - 147
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -
