Interleukin 7 signaling prevents apoptosis by regulating bcl-2 and bax via the p53 pathway in human non-small cell lung cancer cells.
Interleukin 7/Interleukin 7 receptor (IL-7/IL-7R) signaling induces the upregulation of cyclin D1 to promote cell proliferation in lung cancer, but its role in preventing the apoptosis of non-small cell lung cancer (NSCLC) cell lines remains unknown. To study the role of IL-7 in lung cancer cell apoptosis, normal HBE cells as well as A549 and H1299 NSCLC cells were examined using flow cytometry. The results showed that the activation of IL-7R by its specific ligand, exogenous interleukin-7, was associated with a significant decline in apoptotic cells. Western blot and real-time PCR assays indicated that the activation of IL-7/IL-7R significantly upregulated anti-apoptotic bcl-2 and downregulated pro-apoptotic bax and p53 at both protein and mRNA levels. The knockdown of IL-7R through small interfering RNAs significantly attenuated these effects of exogenous IL-7. However, there was no significant anti-apoptotic effect in H1299 (p53-) cells. Furthermore, the inhibition of p53 significantly abolished the effects of IL-7/IL-7R on lung cancer cell apoptosis. These results strongly suggest that IL-7/IL-7R prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax, potentially via the p53 pathway in A549 and HBE cells.
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Zi-Hui
ZH
Liu
Department of Breast Surgery, The Affiliated Hospital of Chengde Medical College Chengde, China.
Ming-Hui
MH
Wang
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Hong-Jiu
HJ
Ren
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Wei
W
Qu
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Li-Mei
LM
Sun
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China.
Qing-Fu
QF
Zhang
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China ; Department of Pathology, The First Affiliated Hospital of China Medical University Shenyang, China.
Xue-Shan
XS
Qiu
Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, China ; Department of Pathology, The First Affiliated Hospital of China Medical University Shenyang, China.
En-Hua
EH
Wang
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C508605:IL7 protein, human; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
Interleukin 7; NSCLC; apoptosis; interleukin 7 receptor; p53