In brief, antibodies against histone isoforms were used to precipitate chromatin in sporo cysts, cercaria and adults. The resulting Cisplatin DNA was ana lyzed either by ChIP Seq or qPCR. ChIP Seq data are available at the NCBI SRA under accessions SRX088545, SRX088544, SRX088543 and SRX087825. For ChIP Seq analysis, a repeat pseudogenome was constructed in which each identified repeat sequence occurred only once. Then SOAP2 was used to align roughly 100,000 36 bp reads for miracidia of two strains, cercaria and adult couples to this pseudogenome. Hit counts for each repeat were normal ized by the total number of aligned reads and compared for the different stages. Introduction p21 was originally identified as a cell cycle regulator through inhibition of different cyclin/cyclin dependent kinase complexes.

p21 is a member of the Cip/Kip family of cell cycle inhibitors, which also includes p27Kip1 and p57Kip2. In addition to its role in cell cycle control, p21 is involved in the regulation of cellular senescence, gene transcription, apoptosis and actin cytos keleton. The role of p21 in breast cancer develop ment and progression has not been fully investigated. While p21 is involved in cell cycle control and is a down stream target of the tumor suppressor p53, it does not fulfill the classic definition of a tumor suppressor. Germline or somatic mutations in the p21 gene are not common in human cancers. Furthermore, in vivo stu dies using p21 knockout mice showed that, while loss of p21 expression efficiently blocked the ability of the cells to undergo G1 arrest following DNA damage, these animals developed normally.

Intriguingly, p21 is often overexpressed in aggressive tumors, including carcino mas of the pancreas, breast, prostate, ovary and cervix. Together these observations suggest that the role played by p21 in cancer is more complex than initially thought and that, in addition to its well known cell cycle regulatory effect, it may have uncharacterized roles in promoting carcinogenesis. Tumor cell migration and invasion are critical steps in the metastatic process and are regulated by numerous tumor secreted factors which modify the tumor microen vironment by acting on stromal recruitment and extracel lular matrix degradation, resulting in tumor cell migration and invasion. Among these tumor secreted factors, TGFb has been shown to play a pivotal role in promoting tumor metastasis.

The TGFb family regu lates asymmetric cell division and cell fate determination during embryogenesis and exerts profound effects on reproductive functions, immune responses, cell growth, bone formation, tissue remodeling and repair throughout adult life. The effects of TGFb in breast cancer are complex. TGFb Drug_discovery is thought to play a dual role in breast cancer progression, acting as a tumor suppressor in nor mal and early carcinoma, and as a pro metastatic factor in aggressive carcinoma.