New Estrogen Receptor Signaling Pathways Regulate The Separation And Identification Of The Factors

Estrogen receptor (ER) is one of the members of the nuclear receptorsuperfamily. Mammalian ER is encoded by two genes:a and ?. Both ERa and ER?can be subdivided into six regions (A-F), which contain two transactivation functionregions, called AF1 and AF2, respectively. AF1 locates in the A/B region, which hasligand-independent transactivation function. AF2 locates in the E/F region, withligand-dependent transactivation function. The effective transactivation of AF1 andAF2 depends on their interaction with other proteins. It has become widely acceptedthat both ERa and ER?can be expressed at the plasma membrane in addition to inthe nucleus, although at a lower density(2-3%) compared with the density in thenucleus. At the membrane, the cross talk with signaling molecules facilitates E2/ER torapidly initiate signal transduction and trigger downstream signaling cascades thatcontribute to important functions. These functions include cell growth andsurvival,migration , and new blood vessel formation. In some instances these resultfrom the initiation of gene transcription, direct stimulation of signaling via G proteinactivation, cAMP generation, phospholipase C activation ,IP3 generation andactivation of extracellular-regulated kinase(ERK), c-Jun N-terminal kinase(JNK) andP38 MAPK(mitogen-activated protein kinase). Furthermore, the nuclear and theplasma membrane form of the ER are believed to be functional complementation,mediating cellular effects rapidly and enduringly. ER plays an important role in thedevelopment of breast cancer. Recently ER is thought to act as a target of the therapyof breast cancer and good index of prognosis. Until now, the endocrine therapy ofmammary carcinoma is acquired mainly by decreasing ER transcriptional activity.Therefore, it is of great significance to discover and characterize the proteins thatmodulateER activityin developing the drugs of diseases related to estrogen.Some evidences have shown that CTGF (connective tissue growth factor) isoverexpressed in pancreatic cancer, breast cancer, and melanoma. CTGF encodes a36-38 kDa cysteine-rich secreted polypeptide that is a member of an immediate earlygene family known as the CCN family. Functioning as matricellular protein, CCNproteins can bridge the functional and physical gap between ECM-associated proteinsand cell surface molecules. Moreover, CCN family proteins can regulate disparatefundamental biological processes, including mitosis, cell adhesion, apoptosis, growth,differentiation, angiogenesis, embtyogenesis, and tumorigenesis by the cross talk withmultiple signal transduction pathways. As a secretory protein, CTGF may play an...