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Isolation of human colon carcinoma cells for resistance to a single interferon associated with cross-resistance to multiple recombinant interferons: alpha, beta, and gamma.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 1990 Mar 21; Vol. 82 (6), pp. 517-22. - Publication Year :
- 1990
-
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-alpha hybrid BBDD (r-IFN-alpha) or recombinant human IFN-gamma (r-IFN-gamma). Surviving variants were designated KM12 alpha R and KM12 gamma R, respectively. KM12 alpha R cells were cross-resistant to the cytostatic and cytolytic effects of r-IFN-alpha, r-IFN-beta, and r-IFN-gamma, whereas KM12 gamma R cells were resistant only to the effects of r-IFN-gamma. 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 KM12 alpha R cell line was not attributable to the loss of specific receptors, because our analyses demonstrated the presence of receptors for IFN-gamma, whereas the KM12 gamma R line lacked specific receptors for IFN-gamma. 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-gamma did not alter its expression. Treatment with r-IFN-gamma induced the expression of manganous superoxide dismutase mRNA in KM12C and KM12 alpha R cells, but not in KM12 gamma R cells, confirming that both KM12C and KM12 alpha R cells, but not KM12 gamma R cells, have functional receptors for IFN-gamma.
- Subjects :
- Blotting, Northern
Carcinoma pathology
Cell Line
Cell Survival drug effects
Colonic Neoplasms pathology
Drug Resistance
Gene Expression
Humans
In Vitro Techniques
Interferon Type I pharmacology
Interferon-gamma pharmacology
Oligonucleotide Probes
Proto-Oncogene Mas
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-myc
RNA, Messenger genetics
Receptors, Immunologic metabolism
Receptors, Interferon
Recombinant Proteins
Superoxide Dismutase genetics
Tumor Cells, Cultured
Carcinoma physiopathology
Colonic Neoplasms physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8874
- Volume :
- 82
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 2138228
- Full Text :
- https://doi.org/10.1093/jnci/82.6.517