Isolation of Human Colon Carcinoma Cells for Resistance to a Single Interferon Associated With Cross-Resistance to Multiple Recombinant Interferons: , beta, and

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Abstract
We established variants resistant to human interferon (IFN) from an IFN-sensitive human colon carcinoma cell line and delineated some of the mechanisms for resistance to IFN-mediated cytotoxicity. The parent KM12C cells were incubated for 2 months in medium containing recombinant human IFN-α hybrid BBDD (r-IFN-α) or recombinant human IFN-γ (r-IFN-γ). Surviving variants were designated KM12α R and KM12γ R , respectively. KM12α R cells were cross-resistant to the cytostatic and cytolytic effects of r-IFN-α, r-IFN-β, and r-IFN-γ, whereas KM12γ R cells were resistant only to the effects of r-IFN-γ. The parent and variant cell lines had similar in vitro growth rates and similar tumorigenicity in male BALB/c nude mice, but the mechanisms for resistance to IFNs differed in the two variant lines. The resistance of the cross-resistant KM12α R cell line was not attributable to the loss of specific receptors, because our analyses demonstrated the presence of receptors for IFN-γ, whereas the KM12γ R line lacked specific receptors for IFN-γ. Northern blot analyses revealed that messenger RNA (mRNA) from the proto-oncogene c-myc was equally expressed in the IFN-sensitive and IFN-resistant cell lines and that treatment with r-IFN-γ did not alter its expression. Treatment with r-IFN-γ induced the expression of manganous superoxide dismutase mRNA in KM12C and KM12α R cells, but not in KM12γ R cells, confirming that both KM12C and KM12α R cells, but not KM12γ R cells, have functional receptors for IFN-γ. [J Natl Cancer Inst 82: 517–522, 1990]

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