Tiwari R K, Wong G Y, Mukhopadhyay B, Telang N T, Liu J, Hakes T B, Osborne M P
Breast Cancer Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Breast Cancer Res Treat. 1991 Mar;18(1):33-41. doi: 10.1007/BF01975441.
Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, as de novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.
除了在细胞培养中具有众所周知的抗病毒作用外，干扰素（IFNs）还对肿瘤细胞具有抗增殖作用。不同干扰素的作用机制尚未完全了解，但近年来已鉴定出许多干扰素诱导基因，这些基因被认为是干扰素作用的介质。在本研究中，我们使用（i）MTT染料形成试验和（ii）软琼脂中的非锚定依赖性（AI）生长，研究了α-干扰素和γ-干扰素对人乳腺癌细胞（MCF-7）的抗增殖作用。发现α-干扰素和γ-干扰素均对MCF-7细胞的生长具有抗增殖作用。此外，还研究了一些干扰素诱导基因的诱导动力学。使用特异性[α-32P]标记的cDNA作为探针，通过mRNA分析测量这些基因的表达。α-干扰素和γ-干扰素对这些基因的诱导是干扰素的主要作用，因为它们的诱导不需要从头合成蛋白质。我们关于α-干扰素和γ-干扰素对这些基因诱导动力学的结果表明，在该细胞系中存在依赖配体的基因激活的复杂机制，其中一些途径相似，一些途径不同。
