Progesterone (PR)
There are three isoforms of PR which are PR-A ,PR-B and PR-C. PR-A is an N- terminally truncated that is crucial for the uterine development and reproductive function. PR-B is needed for normal mammary gland development and PR-C is in default of the classical transcriptional activity instead function as dominant inhibitor of uterine PR-B in the myometrium during labour. ( Carol A. Lange et al 2008)
The active involves the binding with the ovarian steroid ligand, PR gene expression that regulated by the ligand-activated transcription factors can bind directly and indirectly to the DNA. The three PR isoforms are single gene located in the chromosome 11 that undergoes transcription through the alternative promoters and internal translational start site. In the absence of PR, PRs are involved with several chaperone molecules are needed for proper protein folding and are gather of stable PR- hsp90 herterocomplexes that are competent to bind liagand. After binding to the PR, the receptor undergoes restructuring and hsp dissociation. Activation of the receptor will bind directly to the specific PR response element. Binding directly or indirectly bound to the DNA, PR will regulate the basal transcription machinery in conjunction with nuclear receptor coregulatory molecules.( Carol A. Lange et al 2008)
Estrogen (ER)
Estrogen is a modulator of cellular growth and differentiation in the mammary gland. It mediates most of the function through two members of the nuclear receptor superfamily, ERα and ERβ. These receptors are hormone-dependent transcriptional regulators which, in the presence of appropriate ligands, bind to EREs on DNA or interact with proteins in other pathways and affect transcription of specific genes(...
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...cer mainly targeting the ER signalling pathway either by reducing the level of estrogen , antagonizing ER function with antiestrogens such as tamoxifen or down-regulating ER levels with pure antiestrogens such as fulvestrant (Faslodex). ( Rachel Schiff et al 2003)
Tamoxifen is commonly used and is a nonsteroidal SERM, which will inhibit breast cancer growth by competitive blocking of the ER, thus inhibiting estrogen-induced growth. (Elisavet Paplomata et al 2013) Tamoxifen is effective in most patients but there is a complication that causes the presence of ER that does not response to the tamoxifen result in tamoxifen resistance. Some patient that initially response to tamoxifen will acquired tumour resistance will lead to tumour progression and death. When the patient develops tamoxifen resistance, the treatment must stop immediately. (Rachel Schiff et al 2003)
Women who inherit a mutation in one copy of BRCA1 or BRCA2 are at high risk of developing breast and ovarian cancers6. This could be due to the disruption in the pathway of BRCA proteins in the cell nucleus. If BRCA1 is defective, it loses its ability to fix damaged DNA and causes tumor. It is because once the defective BRCA1 raises, it allows the cells to develop and divide uncontrollably. Since defective in BRCA1 causes cancers, it is important to understanding the function of the protein by analyzing its sequence and structure.
To determine trends in Birth weights, APGAR scores and NICU stay of the neonates born to PCOS mothers.
..., t. t. (n.d.). Menopausal Hormone Replacement Therapy Use and Cancer - National Cancer Institute. Comprehensive Cancer Information - National Cancer Institute. Retrieved September 19, 2011, from http://www.cancer.gov/cancertopics/factsheet/Risk/menopausal-hormones/print
Transcription factors are proteins that help turn specific genes "on" or "off" by binding to nearby DNA.
Many breast cancers are sensitive to the hormone estrogen. Thus estrogen leads to development of breast cancer tumor formation. Such cancers have cell surface receptors for estrogen. They are called ER-positive cancer or estrogen receptor-positive cancer.
This is due to the fact that the binding of a ligand to this receptor triggers processes which change the synthesis of proteins, such as enzymes, through gene transcription in order to bring about a response at a cellular level [5]. An example of a drug that acts on this receptor is Pazopanib, which Stenberg [6] states acts on vascular endothelial growth factor and platelet derived growth factor receptors as well as c-Kit to block tumour growth and inhibit
Vogel, VG (May 2008). Preventing breast cancer in high-risk women, 2008. Oncology, 22, 6. p.666. Retrieved from Academic OneFile
...nosis of this disease, but the administration of Herceptin proved to effectively inhibit the activity of the receptor and thus lead to improved health status. Currently Trastuzumab is normally used in this type of breast cancer, but first this receptor overexpression must be identified to assure effectiveness of treatment because there are different receptors associated with different type of breast cancer such as BRCA1, BRCA2 or ER positive for which other treatment must be applied. As on the market are approved several drugs against breast cancer physician can perform pharmacogenetic test to determine which drug would best suit the patient. The same way of choosing adequate drug will be performed in other type of disease.
Menopausal Hormone Replacement Therapy, once believed to ward off heart disease, osteoporosis, and cancer, while improving women’s quality of life, has now been confirmed to pose serious risks and increase the threat of developing various health conditions with long-term use. To many suffers of menopausal symptoms, the palliative benefits of hormone products outweigh the risks. The U.S. Food and Drug Administration (FDA) currently advise women to use menopausal hormones conservatively for the shortest time and at the lowest dose possible to control symptoms. Concurrent studies governed by the FDA are in the works to determine the safety and effectiveness of alternatives in treatment of menopausal symptoms without hormone products. (USDHH)
A USC researcher is interested in the roles of coregulators in steroid hormone regulation of transcription in cancer cells and would like to write a grant proposal on this topic. The two key coregulators of interests are Hic-5 and G9a. As he is preparing the proposal, he hopes to find information about the following questions:
Hormonal or endocrine therapy can be used to treat metastatic, hormone-receptor-positive breast cancer. Since the early 1970s, the ER antagonist, tamoxifen has been used to inhibit or suppress tumour growth (20). The selective oestrogen receptor modulator (SERM) works by preventing the binding of oestrogen to oestrogen receptors located in the breast tissue (20). In order to exhibit its antagonistic effects, it undergoes metabolism by cytochrome P450 enzymes and converted into its active and inactive metabolites (Figure 4) (20). The active metabolites of tamoxifen are N-desmethyltamoxifen, which can be converted to endoxifen by CYP2D6, as well as 4-hydroxyltamoxifen (Figure 4) (20). Consequently, the affinity of these active metabolites to the ER is increased by ten-fold compared to its parent compound (20).
Gonadotrophins are hormones that play a role in targeting certain structures in the Reproduction system. In females, they affect the ovaries and are produced during the menstrual cycle by the pituitary gland stimulation. There are two classes of gonadotrophins; follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH targets the follicles in the ovaries, preparing them for growth and development. LH’s primary function is to aide in the maturation of eggs, prior to ovulation. ?
binding protein found primarily in the hair cell, is said to contribute to the development
Breast cancer is so prevalent in women because with the development of breasts in young girls during the ages of 11 - 14, breast...
Campbell N. A., Reece L. A., Cain M. L., Wasserman S. A., Minorsky P. V. and Jackson R. B. (2008). Regulation of Gene Expression