It is not necessarily YY 1 — the frequently forgotten

de Nigris et al. (1) performed an interesting study on the functional implication of YY1 in the VEGF regulatory network, leading to a rationale for using YY1 as a therapeutic target molecule in cancer therapy. However, considering the application of YY1 for antiangiogenic treatment bears a fundamental risk because the observed effects are not necessarily specific for YY1: the YY1 antibody (C-20, sc-281, Santa Cruz Biotechnology) used for (chromatin-) immunoprecipitation experiments and Western blotting does not detect exclusively YY1 but also the highly homologous YY2 transcription factor, as previously shown (2). Notably, increasing evidence is given that YY2 is regulated specifically and independently of YY1 (3), and, if both factors are expressed within a particular cell, they can compete for the same regulatory element, frequently mediating antagonistic transcriptional effects (2, 4). Because YY2 is evolved from a retroposition event of the YY1 gene (5), the second technical concern is a matter of the (commercial) siRNA against YY1. The exact sequence has not been provided by the authors (or in the literature they refer to) so that crossspecificity on YY2 RNA cannot yet be excluded. Before a final conclusion that YY1 represents a crucial molecular target for antiangiogenic therapy in cancer, confirmatory experiments on the specific effects of YY1 are required. However, we agree with de Nigris et al. that Yin-Yang transcription factors deserve highest interest regarding their implication in cancer biology.