NF-κB acts downstream of EGFR in regulating low dose cadmium induced primary lung cell proliferation.
Apart from cytotoxicity cadmium has no special attributes towards cell's physiological function. The role of cadmium with respect to cell growth is still under debate. Mitogen activated protein kinase and Ca(2+)/calmodulin dependent protein kinase dependent pathways are the two elaborately studied concerning cadmium induced cell proliferation. Low concentration of cadmium chloride (2.5 μM) was applied to mice primary lung epithelial cells and cell proliferation was measured both by cell cycle analysis and Brdu incorporation assay. Effects of differential dose of cadmium chloride on lung epithelial cells were evaluated morphologically by atomic force microscopy. RT-PCR and western blot altogether corroborated the specific signalling pathways concerning cadmium induced lung cell proliferation. Cadmium induced lung epithelial cells which over-expressed EGFR, were transfected with siEGFR, revealed downstream molecules and RNAi induced EGFR silencing. Use of siEGFR effectively prevents expression of proinflammatory and cell proliferative markers. Moreover N-acetyl cysteine and ascorbic acid mediated inhibition of EGFR and downstream signalling molecules indicate the involvement of reactive oxygen species. Exposure to low concentration of cadmium promotes the growth of primary mice lung epithelial cell by EGFR signalling. We have also transfected the primary lung epithelial cell with siRNA against the regulatory subunit of nuclear factor-κB (NF-κB) and the data shows that cadmium induced lung cell proliferation is the effect of EGFR mediated NF-κB activation.
Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, West Bengal, India.
Subhadip
S
Kundu
Suman
S
Sengupta
Arindam
A
Bhattacharyya
D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D019256:Cadmium Chloride