Human renal cancers resistant to IFN's antiproliferative action exhibit sensitivity to IFN's gene-inducing and antiviral actions.
OBJECTIVE
Although treatment with interferon-alpha (IFN alpha) results in tumor regression in a subset (< 20%) of patients with renal cell carcinoma, the underlying mechanisms for the resistance of renal cancer (RC) cells to IFN alpha is unknown.


METHODS
We examined 5 RC lines resistant and 5 RC lines sensitive to the antiproliferative effects of IFN alpha for differences in: 1) the number of IFN binding sites, 2) the number of signal-transducing IFNAR-1 chains of the IFN alpha receptor, 3) IFN alpha receptor structure, 4) IFN-stimulated gene (ISG) expression and 5) IFN alpha sensitivity in antiviral assays.


RESULTS
No structural alterations in the IFN alpha receptor were detected in any RC line examined, although varying numbers of ligand binding sites and IFNAR-1 signal transducer chains were present. All 5 IFN-sensitive, and 4 of 5 IFN-resistant RC lines were sensitive to the antiviral and gene-inducing actions of IFN alpha.


CONCLUSIONS
The resistance of RC lines to IFN's antiproliferative action is not due to defects in ligand binding or in IFN-receptor structure. Our results indicate that the defective antiproliferative response in most RC cells is not due to their failure to induce the gene-inducing and antiviral effects of IFN alpha.
Pfeffer
L M
LM
Department of Pathology, University of Tennessee Health Science Center, Memphis 38163, USA.
Wang
C
C
Constantinescu
S N
SN
Croze
E
E
Blatt
L M
LM
Albino
A P
AP
Nanus
D M
DM
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001665:Binding Sites; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000503:physiopathology / Q000628:therapy* / Q000821:virology; D002455:Cell Division; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000628:therapy* / Q000821:virology; D017471:Receptors, Interferon; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007370:Interferon Type I; D017471:Receptors, Interferon; D011994:Recombinant Proteins