Sharma H W, Perez J R, Higgins-Sochaski K, Hsiao R, Narayanan R
Division of Oncology, Roche Research Center, Hoffman-La Roche Inc., Nutley, NJ 07110, USA.
Anticancer Res. 1996 Jan-Feb;16(1):61-9.
Antisense inhibition of the RelA subunit of NF-kappa B transcription factor (but not the NFKB1 subunit) causes pronounced inhibition of tumor cell growth in vitro and in vivo. Inhibition of either subunit, however, results in inhibition of the heterodimeric NF-kappa B complex in antisense-treated cells. Either of the subunits of NF-kappa B can form homo- or heterodimers with other members of the Rel oncogene family. In an effort to decipher the role of homo- vs heterodimeric NNF-kappa B in regulating tumor cell growth, we have used a decoy approach to trap these complexes in vivo. Using double-stranded phosphorothioates as a direct in vivo competitor for homo- vs heterodimeric NF-kappa B, we demonstrate that decoys more specific to RelA inhibit growth tumor cell growth in vitro. We demonstrate that RelA, either as a homodimer or a heterodimer with some other members of the Rel family and not the classical NF-kappa B (RelA/NFKB1), is involved in the differential growth control of tumor cells. Our results indicate that such transcription factor decoys can be a non-antisense tool to study the function of DNA-binding transcription factors.
对核因子-κB转录因子的RelA亚基（而非NFKB1亚基）进行反义抑制，可在体外和体内显著抑制肿瘤细胞生长。然而，抑制任一亚基都会导致反义处理细胞中的异二聚体核因子-κB复合物受到抑制。核因子-κB的任一亚基均可与Rel原癌基因家族的其他成员形成同二聚体或异二聚体。为了阐明同二聚体与异二聚体核因子-κB在调节肿瘤细胞生长中的作用，我们采用了一种诱饵方法在体内捕获这些复合物。使用双链硫代磷酸酯作为同二聚体与异二聚体核因子-κB的直接体内竞争物，我们证明对RelA更具特异性的诱饵在体外可抑制肿瘤细胞生长。我们证明，RelA无论是作为同二聚体还是与Rel家族的其他一些成员形成异二聚体，而不是经典的核因子-κB（RelA/NFKB1），都参与了肿瘤细胞的差异生长控制。我们的结果表明，这种转录因子诱饵可作为一种非反义工具来研究DNA结合转录因子的功能。
