The striking 3 4 1 male predominance of ESCC was previously ascribed to the different patterns of smoking and drinking between males and females. However, more recently Bodelon et al. reported that current users of es trogen and progestin therapy show reduced risk of selleck screening library ESCC. Previous research supports this finding as several groups have reported estrogen induced gene regulation in esophageal squamous cell carcinoma and Barretts esophageal adenocarcinoma. Moreover, Wang et al. specifically demonstrated that serum level of estradiol of ESCC patients from the high risk areas were significantly lower compared to healthy controls from both high and low risk areas and suggested the use of estrogen analogues as promising targets for the prevention and treatment of ESCC.

Additionally, published scientific data shows that estrogen induces an inhibitory effect on esophageal carcinoma by activating the estrogen receptor. The activated ER func tions as a transcription factor that binds to a specific TFBS known as the estrogen response element. There are two ER subtypes, ER and ERB, that are encoded on human chromosomes 6q25. 1 and chromosome 14q22 24, respectively. Both ER and ERB bind to the same EREs, but ER does so with an ap proximately twofold higher affinity. Additionally, ERB is known to bind to ER suppressing ER function. The inverse biological effect associated with the two ER subtypes has been confirmed to exist in ESCC. This collation of research findings suggests that the estrogen based therapies which have improved survival rates of cancer types such as prostate cancer, lung cancer, brain and spinal cord tumors, and breast cancer, may also improve the outcome of ESCC.

Our current study aims at identifying estrogen respon sive genes by using ESCC as a model. Anacetrapib Potentially, such selleck catalog genes could be affected by estrogen. We propose a methodology that provides insight into the underlying regulation of estrogen responsive ESCC genes. We mapped EREs to the promoters of 418 ESCC genes using the Dragon ERE Finder version 6. 0. The 418 ESCC genes were divided into two groups 1 genes whose promoters contain pre dicted EREs, and 2 genes lacking predicted EREs. These two gene groups were further divided into those known to be experimentally confirmed as estrogen responsive and those that are not. To accomplish this the 418 ESCC genes were cross checked against two databases housing estrogen responsive genes, namely KBERG and ERtargetDB databases. At the time of analysis the KBERG database contained 1516 experimentally confirmed estrogen responsive genes. The ERTargetDB database contained 40 genes with 48 experimentally verified ERE direct binding sites and 11 experimentally verified ERE tethering sites.