Breast cancer is one of the most common and important diseases that affect women and ovarian cancer is the fourth most common cause of cancer mortality in American women1. These cancers are triggered by germline mutations on the C-terminal of a gene called BRCA1 (or “Breast Cancer 1, Early Onset Gene”) tumor suppressor. The BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, consists of 24 exons and encodes a multidomain protein of 1863 amino acid residues in human2. The BRCA1 proteins produced from BRCA1 gene help preventing cells from growing and dividing too rapidly or in an uncontrolled way3. The family of BRCA1 genes is called RING-type zinc fingers or RNF. The BRCA1 protein is characterized within the superfamily of Rad9-like proteins which consist of C-terminal BRCT repeats that assist in the binding of phosphorylated proteins in the DNA damage response and DNA repair4. Like many other genes involved in familial cancer, BRCA1 appears to encode a tumor suppressor, a protein that acts as a negative regulator of tumor growth1. BRCA1 proteins are important in genomic stability so loss of their function can cause genetic instability which lead to tumourigenesis. Thus, the sequence of BRCA1 protein is analyzed to the understanding the protein’s function in the development of the cancers.
The sequence of BRCA1 protein shows that there are quite a few of cysteine residues. These cysteine residues form disulfide bonds which help stabilize the secondary structure of the protein. The secondary structure of BRCA1 protein indicates that there are alpha helices and beta turns which are connected by loops and turns. The 3D structure of BRCA1/BARD1 RING-domain heterodimer is shown in figure 1.
Figure 1...
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... Thus, the loss of BRCA1 can result in defective DNA damage repair, abnormal centrosome duplication, cell-cycle arrest, growth retardation, increased apoptosis, genetic instability and tumorigenesis2. The study of BRCA1 mutation in mice may be used for new therapeutic approaches, although the cause of the mutation in BRCA gene is unclear.
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.
"The Species of the Secondary Protein Structure. Virtual Chembook - Elmhurst College. Retrieved July 25, 2008, from http://www.cd http://www.elmhurst.edu/chm/vchembook/566secprotein.html Silk Road Foundation. n.d. - n.d. - n.d.
The underlying purpose of the experiments performed in the study, Promoter Hypermethylation of KLF4 Inactivates its Tumor Suppressor Function in Cervical Carcinogenesis, is to investigate the mechanism by which the KLF4 gene is silenced in cervical carcinomas. Cervical cancer accounts for 250,000 female deaths every year. Developing therapies for cervical cancer has been limited due to the lack of genetic and epigenetic data of the mechanism causing the cancer. The KLF4 gene is a transcriptional regulator of cell growth and differentiation. It functions as a tumor suppressor in cervical cancer, but is found to be inactivated in cervical cancer. The overexpression of KLF4 protein is known to inhibit cervical cancer cell growth and tumor formation by activating a cell cycle suppressor. Promoter CpG island hypermethylation can result in transcriptional silencing of many tumor suppressing genes. Two CpG regions, BSQ1 and BSQ3, were examined in this experiment.
A mutation in the BRCA1 or BRCA2 gene is associated with an increased risk of ovarian cancer
About 12% of women in the United States will develop breast cancer in their lifetime, more than any other type of cancer (www.breastcancer.org, 2015). Many people lack the knowledge of how breast cancer is developed. Some people think they will not get cancer because they do not smoke cigarettes, but this is not the only cause of cancer developing in the breast. Anyone can get cancer. Everyone is potentially at risk for developing some form of Cancer (American Cancer Society, 2015).
The cell cycle is the process by which cells progress and divide. In normal cells, the cell cycle is controlled by a complex series of signaling pathways by which a cell grows, replicates it’s DNA and divides, these are called proto-oncogenes. A proto-oncogene is a normal gene that could become an oncogene due to mutations. This process has mechanisms to ensure that errors are corrected, if they are not, the cells commit suicide (apoptosis). This process is tightly regulated by the genes within a cell’s nucleus. In cancer, as a result of genetic mutations, this process malfunctions, resulting in uncontrolled cell proliferation. Mutations in proto-oncogene or in a tumour suppressor gene allow a cancerous cell to grow and divide without the normal control imposed by the cell cycle. A change in the DNA sequence of the proto-oncogene gives rise to an oncogene, which
...reasing the 5-years survival and increasing the death worldwide due to cancer; but can be explained by increased life anticipation, since cancer incidence increases with age, and to remarkably increasing in lung cancer incidence rates References BRCA1 and BRCA2: Cancer Risk and Genetic Testing Fact Sheet.... (2014). Retrieved on April 18, 2014, from Gene mutations that can lead to cancer (Society, 2014).
There are many different approaches for management of breast cancer and treatment options that patients may select in collaboration with health care providers. Breast cancer is a complex disease that presents in many different types, with specific biological features unique to each patient. Invasive cancers are classified based on tumor type and histological grade, which is of utmost importance when deciding the course of treatment. Contemporary advances in breast cancer treatments have been made, especially in chemotherapy, hormone and biological therapies. Treatment can be a combination of local treatments, systemic treatments, and in some cases, new targeted treatments (Watts, 2013).
The American Cancer Society publishes current advances made in cancer research on their website. Many of the exciting discoveries about how best to treat the disease focus on the genetic aspects associated with certain types of cancer. In addition, treatments aimed at genetic solutions to cancer may be more effective and may cause fewer adverse side effects than traditional cancer treatments (American Can...
...bic, they are able to bind to the exposed hydrophobic surface of the non-native polypeptide. Mutations which substitute these non-polar amino acids with polar residues result in the abolition of polypeptide binding.
The covalent structure of a protein is composed of hundreds of individual bonds. Because free rotation is possible around a good portion of these bonds, there are a very high number of possible conformations the protein can assume. However, each protein is responsible for a particular chemical or structural function, signifying that each one has a distinctive three-dimensional configuration. By the early 1900’s, numerous proteins had been crystallized. Because the ordered collection of molecules in a crystal can only form if all of the molecular units are the same, the discovery that proteins could be crystallized proved that even large proteins have distinct chemical structures. This deduction completely transformed the understanding of proteins and their respective functions. It is important to investigate how a series of amino acids in a polypeptide chain is translated into a three-dimensional protein structure. There are five general topics related to this process: the structure of a protein is determined by its amino acid sequence, the role of a protein is dependent on its unique structure, an isolated protein typically exists in a small number of stable forms, non-covalent interactions are the most important stabilizing forces in a protein structure, and there are structural patterns that aid in explaining and understanding protein architecture.
There are four main levels of a protein, which make up its native conformation. The first level, primary structure, is just the basic order of all the amino acids. The amino acids are held together by strong peptide bonds. The next level of protein organization is the secondary structure. This is where the primary structure is repeated folded so that it takes up less space. There are two types of folding, the first of which is beta-pleated sheets, where the primary structure would resemble continuous spikes forming a horizontal strip. The seco...
Uterine cancer is an important women health problem developing rapidly, killing over 200,000 women each year. No one has discovered the actual cause, but there is a leading factor that has great suspicions to what is causing this cancer to grow rapidly.
A polypeptide chain is a series of amino acids that are joined by the peptide bonds. Each amino acid in a polypeptide chain is called a residue. It also has polarity because its ends are different. The backbone or main chain is the part of the polypeptide chain that is made up of a regularly repeating part and is rich with the potential for hydrogen-bonding. There is also a variable part, which comprises the distinct side chain. Each residue of the chain has a carbonyl group, which is good hydrogen-bond acceptor, and an NH group, which is a good hydrogen-bond donor. The groups interact with the functional groups of the side chains and each other to stabilize structures. Proteins are polypeptide chains that have 500 to 2,000 amino acid residues. Oligopeptides, or peptides, are made up of small numbers of amino acids. Each protein has a precisely defined, unique amino acid sequence, referred to as its primary structure. The amino acid sequences of proteins are determined by the nucleotide sequences of genes because nucleotides in DNA specify a complimentary sequence in RNA, which specifies the amino acid sequence. Amino acid sequences determine the 3D structures of proteins. An alteration in the amino acid sequence can produce disease and abnormal function. All of the different ways
Ninety percent of deaths from tumor are due to metastasis making the pathophysiology of this process and study of genes involved regulating metastasis central to understand the mechanism of this disease (Boimel et al., 2011). Breast cancer seems to originate from changes in the architectural breast tissue organization consequent to interaction between cell genome and extracellular environment. Thus basic cellular processes and their molecular regulation play an important role on the onset of breast cancer. Various transcription factors are involved in regulation and expression of specific genes crucial for cellular mechanism; any alteration in these mechanisms may give rise to series of malignancies including breast cancer (Cantilte et al.,
Breast Cancer is something that terrifies not only myself but most of the females in my family as well. My grandmother had breast cancer that caused her to passed away early. I have three aunts and many cousins that may be in danger of getting of getting breast cancer. And since most of them live in Ethiopia, Africa the incidence of the disease is higher. It is very important to me to educate myself in the causes and effects of breast cancer as well as the treatment. I want to know what possible treatment there is available for this that might help either me or anyone in my family to fight back and give us hope that we can beat it.