Increase of epidermal growth factor receptor expression associated with a lack of antiproliferative effect of IFN-beta in human lung cancer nodules in organotypic culture.
The possible relationship between the effects of alpha 2-, beta- and gamma-interferons (IFNs) on the growth of alveolar II pulmonary tumor cells (A549) maintained in tridimensional organotypic culture (nodules) and the modulation of epidermal growth factor receptor (EGF-R) expression was investigated. Treatment with rHu IFN-alpha 2 or IFN-gamma which results in the inhibition of the growth of A549 nodules had no effect on the binding of 125I-EGF to these cells. In contrast, treatment with rHu IFN-beta which exhibits no antiproliferative activity on A549 nodules resulted in a reproducible increase of the binding of 125I-EGF. Scatchard analysis of the EGF binding data indicated that a 48-hour exposure period resulted in an increase in the apparent number of cell surface EGF-R but did not significantly alter receptor affinity. Results from Northern blot analysis showed that the enhanced expression of EGF-R on the A549 nodule cells treated with IFN-beta correlates with an increase in mRNA for EGF-R. No modification of the EGF-R mRNA expression was observed in nodules treated with IFN-alpha 2 or IFN-gamma. In this model, our results suggest a relationship between resistance to antiproliferative effect of IFN-beta and modulation of EGF-R.
Martyré
M C
MC
U196 INSERM, Institut Curie, Paris, France.
Grimaux
M
M
Beaupain
R
R
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins
D007370:Interferon Type I; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D007371:Interferon-gamma; D066246:ErbB Receptors