A dominant negative PBX1 protein or HOX hexapeptide motif that disrupted the interaction between PBX1 and HOX was found to significantly reduce the proliferation of these cancer cells. Moreover, PBX1 acts as a pioneer factor in breast cancer, remodeling the chromatin to favor the recruitment of estrogen receptor alpha. PBX1 has also been demonstrated to be a downstream effector of the Notch signaling pathway, which is frequently activated in ovarian, cervical, and certain types of breast carcinomas. In light of the potential role of PBX1 in various cancer types, identifying the PBX1 transcription target genes in cancer cells is critical to elucidating its oncogenic mechanisms. The homeobox gene family, which is critical in transcriptional regulation, encodes nuclear proteins containing highly conserved DNA-binding homeodomains. Homeobox proteins are involved in critical activities during development and tumorigenesis. In this report, we focused on one of the homeobox genes, PBX1, which was found to play a critical role in ovarian cancer, with the intent of identifying and characterizing its transcriptional network in cancer cells. Integrating analysis of gene promoters bound by PBX1 and the PBX1 transcriptome allowed us to identify genes directly regulated by PBX1. The robustness of our genome-wide ChIP-chip assay is evidenced by the observation that the canonical PBX1 motif is highly enriched in the PBX1 ChIPed sequences. We have demonstrated that 195 PBX1 ChIP targets significantly Sertraline hydrochloride overlapped with promoter occupancy of RNA polymerase II and H3K4me3, a histone mark associated with active transcription, but not with H3K27me3, a histone mark associated with transcription repression. In addition, we found that ChIP targets were significantly enriched only among genes whose transcription is supported by PBX1 but not among genes whose transcription is suppressed or not affected by PBX1. These data taken together support the view that PBX1 primarily serves as a transcriptional activator rather than a repressor in ovarian cancer cells. Further experiments should be performed to determine if other cofactors serve as co-regulatory factors with PBX1 in cancer cells. It can be envisioned that this positive auto-regulatory loop operates to ensure sustained transcriptional activity of other PBX1 regulated genes. The results as reported here represent a first step toward understanding the complex regulatory network of PBX1 in carcinomas. As the role of PBX1 in human solid tumors is emerging, the target genes directly controlled by PBX1 reported herein will serve as footsteps for deciphering how PBX1 contributes to tumor development. This study also raises several important questions yet to be addressed. For example, it would be interesting to test whether the PBX1 regulated genes identified in ovarian carcinoma are shared with the machinery operating during organ development. Since overexpression of PBX1 and MEOX1 is relatively specific to ovarian cancer as compared to other solid tumors, the biological significance of PBX1 and MEOX1 co-expression and their cooperation in transcriptional regulation are Catharanthine likely to be context- and tissue-dependent. From this perspective, it would be important to determine if MEOX1 modulates the selectivity and target sequence binding affinity of the PBX1 transcription complex in ovarian cancer, and ultimately, it would be interesting to determine how PBX1/MEOX1 complex formation promotes oncogenesis. Multiple ongoing studies aim at improving the Ab vaccination strategy.