Oncogenes and Breast Cancer - Article Example

Oncogenes and Breast Cancer” Proto-oncogenes act as normal genes for cell division and differentiation. Alteration of these genes due to mutation converts them to the oncogenes. As cancer is emerging as one of the leading causes of death in developed as well as developing nations, research is going on to recognize and typify the factors influencing mutations that pave the way for the onset of tumorigenesis; since the aetiology of the cancer is a multifaceted understanding interaction of these factors becomes crucial. Studies reveal that tumorigenesis is responsible for proliferation of cancer. In case of breast cancer a variety of proto-oncogenes, such as c-myc, c-erbB-2/neu have been identified. After the human genomic project, research has taken new paradigms to understand the gene-expression and analysis. Thus, classification of tumors in diverse types and subtypes along with the identification of individuals who are at the potential risk of cancer is gaining prevalence. A combination of data procured from gene-expression and genomic information aids in the detection of possible new targets for designing high-throughput screening strategies for designing drugs that will lead to advances in cancer cell-targeted therapy. The present article deals with the importance of understanding for oncogenes to comprehend breast cancer. Introduction Cancer is known as malignant neoplasm, the hallmark characteristic involves uncontrolled proliferation of cells. Under normal conditions cells grow, divide and die, but in a genetic defect called mutation occur in cancer cells leading to the formation of an abnormal DNA. As genes are the basic control machine of the cells, alteration of any kind may bring devastating consequences, or malignancy. When compared with the normal cells, where damage of any kind is taken care by the repair system, tumor cells do not have any repair mechanism for the damaged DNA and there is a constant proliferation of cells without displaying senescence hence, generating a series of abnormal cells, with altered cellular pathways for uncontrolled proliferation, figuring malignant tumors (Alberts 2007; Katzang et al. 2009). (Normal cell cycle) (Genetic mutation- causes alteration in genes) (Alberts 2007) Cancer cells manifest, to varying degrees, four characteristics that distinguish them from normal cells, comprising- uncontrolled proliferation, de-differentiation and loss of function, invasiveness and metastasis (Rang et al. 2007). The Genesis of a Cancer Cell A normal cell turns into a cancer cell because of one or more mutations in its DNA, which can be inherited or acquired. In case of the breast cancer, woman who inherits a single defective copy of either of these tumor suppressor genes BRCA1 and BRCA2 displays an augmented risk of developing breast cancer. However, carcinogenesis is a complex, multistage process, usually involving more than one genetic change. Other epigenetic factors responsible for carcinogenesis involve epigenetic factors, such as level of hormones in the body, exposure to carcinogens and tumor promoting agents. These epigenetic factors do not produce cancer by themselves but enhances the likelihood of genetic mutation(s) resulting in cancer. These genetic changes are categorized as - A. The activation of proto-oncogenes to oncogenes: Proto-oncogenes are the normal genes present in the cells and are responsible for controlling cell division, cell differentiation and apoptosis. A triggering factor such as a virus or exposure to any carcinogen brings malignant changes in the cell. B. The inactivation of tumor suppressor genes: A cell has the mechanism to protect itself from uncontrolled proliferation and tumor formation due to expression of genes called tumor suppressor genes. These genes possess the ability to suppress malignant changes and are also referred as antioncogenes. Mutation in proto-oncogenes or tumor suppressor genes results in the proliferation of tumor. Thus, a loss of function of tumor suppressor genes can be the critical event in carcinogenesis (Rang et al. 2007; Katzang 2009). More than 30 tumor suppressor genes as well as more than 100 dominant oncogenes have been found to be associated with various types of cancers (Rang et al. 2007). Characteristics of Cancer cells The genetic basis of cancer has been revealed through numerous animal models. The Cancer Genome Atlas aims at methodically differentiating the configurational source of cancer, through recognition of the genomic mutations linked with every cancer form. A corresponding progress and description forms the basis of understanding growth and external appearance of the cancer or tumor called the phenotype of the cancer, is essential for designing drugs that can potentially target the cancer cells (Luo 2008). The special characters of cancer cells is uncontrolled proliferation which is the result of various cellular alterations encompassing- growth factors, receptors and signalling pathway; the cell cycle transducers like cyclins, cyclin- dependent kinases (cdks) or the cdk inhibitors. The apoptotic machinery normally disposes abnormal cells, telomerase expression, and local blood vessels resulting from tumor-directed angiogenesis. Possibly, all the genes coding for these components could be categorized as tumor suppressor genes or the oncogenes, but not all the genes are prone to malignant transformation required for the proliferation of cancer (Katzang 2009; Rang et al. 2007). Proliferation of Cancer Cells Proto-oncogene are converted into oncogenes such as sis, erbB, ras, myc, gene for cyclin D etc and results in uncontrolled proliferation and de-differentiation of cells. On the other hand, decrease in the expression of tumor suppressor genes, p53, Rb1 etc causes diminished apoptosis and alteration in the telomerase. Such alterations result in the development of primary tumor followed by production of metalloproteinase, at this stage tumor invades nearby tissues. Further proliferation causes angiogenesis followed by metastasis and development of secondary tumors, indicating the fact that genesis of cancer is multifactorial as it involves more than one genetic change and action of promoters, co-carcinogenic factors and hormones. Cancer is not inherited but it is the mutated gene which is inherited and is responsible for causing cancer (Katzang 2009; Rang et al. 2007). Proto-oncogenes and their products associated with breast cancer: Genes for growth factors e.g. IGF and its product, IGF; gene for EGF receptors (e.g. c-erbB) and its product her2/neu; c-ras and its product the Ras protein; c-src and its product Cytoplasmic tyrosine kinase are responsible for inducing breast cancer (Katzang 2009; Rang et al. 2007). Breast Cancer The BRCA-1, BRCA-2, p53, ATM (ataxia telangienctasia mutated), HER-2/neu oncogene are the major contributing gene for the development of breast cancer. Cancer cell lines show their amplification from 2- 20 fold. The degree of amplification is significant to envisage the survival time of the patient as well as the chances of cancer relapse; highlighting the fact that genes play an imperative role in breast cancer pathogenesis (All About Breast Cancer Genes). Breast cancer is categorized as A. Ductal carcinoma the most common type of cancer and is not invasive but turn to be invasive if not treated and B. Lobular carcinoma- is invasive in nature. Risk factors and causes encompass-1. Age and gender- normally women are prone for developing breast cancer around 50 years of age. 2. Family history may play an imperative role in inducing breast cancer as a defective gene inherited enhances the chances of breast cancer. 3. Menstrual cycle- If the menstrual cycle began early, before the age of 12 or the menopause is late, after the age of 55, the chances of breast cancer are higher. Other risk factors include, alcohol consumption, women who never had any children or had after the age of 30; women who consumed diethylstilbestrol (DES) to avoid miscarriage; obesity- as it elevates the concentration of estrogen levels, women undergone hormone replacement therapy or exposure to radiation either in the breast development phase or earlier stage of life (Carlson et al. 2009; Chlebowski et al. 2009). Symptoms- Development of a lump with uneven margins, change in the appearance of the breast, redness or dimpling provides suspicion, discharge from the nipples, pain in bone, ulcer on the skin, swelling in arm, loss of weight are a few symptoms that are alarming for the individual to go for medical checkup (Carlson et al. 2009; Chlebowski et al. 2009). Treatment of breast cancer includes two categories- A. Early stage treatment when tumors are confined to breast, B. late stage treatment when tumors start moving and invading other body parts depending on the condition of the patient treatment involves-A. Local Treatments including 1. Surgery involves breast-conserving surgery or lumpectomy, mastectomy and dissection of lymph node. The side effect involves- damage of nerves, weight shift, lymphedema, tenderness, discomfort in incision site and soreness of breast. 2. Radiotherapy- is a targeted therapy to abolish cancer cells that adhere around the incised area. Radiotherapy diminishes the chances of breast cancer by 70%. Individuals may tolerate the therapy as the side-effects are confined to the treated region. B. Systemic treatments comprise 1. Chemotherapy- deals with medication provided to weaken and subsequently destroy the cancer cells; it affects the entire body the route of action is through blood. As the drugs target rapidly dividing cells, therefore drugs also target normal blood cells, mouth, intestinal tract, hair. The intensity of side effects directly depends on the amount of medicines being taken. 2. Hormonal therapy- levels of estrogen and progesterone is essential to check the growth of the cancer cells. Hormone therapy targets estrogen and prevent the binding of estrogen with cancer cells or through the procedure of ovariectomy or oophorectomy (Cancer compass; Breast cancer: Treatment). Diagnosis, Prevention and Management of Breast Cancer: Suspected mass (2 cm) Diagnosis tissue diagnosis Bilateral mammogram Diagnostic and surgical lumpectomy Pathology assessment (histology+ diagnosis + margins) If positive margins, then adequate surgery or mastectomy (Guidelines for the Management of Breast Cancer). Conclusion Cancer is curable in the present epoch if it is diagnosed in the early stages. The article deals with the genetic aspects, the risk factors associated with the cancer along with the symptoms diagnosis and management of the breast cancer. It is necessary to avoid direct exposure to the carcinogens as they may trigger the conversion of proto-oncogenes to oncogenes which are responsible for altering the cellular physiology as well as morphology. Management of breast cancer required intense observation and perseverance. References 1. Alberts B., Johnson A., Lewis J., Raff M., Roberts K., &Walter P. (2007). Molecular Biology of the Cell. 5th ed. Garland Science. 2. Katzang B.G., Masters S.B., &Trevor A.J. (2009). Basic & Clinical Pharmacology. 11th ed. Tata McGraw Hill Education Private Limited. p. 935- 937. 3. Rang H.P., Dale M.M., Ritter J.M., Flower R.J. (2007). Rang and Dales Pharmacology. 6th ed. Churchill Livingstone Elsevier. p. 719 4. All about Breast Cancer Genes. (n. d.). Retrieved from http://www.lbl.gov/Education/ELSI/Frames/cancer-genes-f.html. 5. Cancer Compass. (n. d.). Retrieved from http://www.cancercompass.com/learn/cancer-information/breast-cancer/treatment/hormone-therapy 6. Carlson R.W., Allred D.C., Anderson B.O., Burstein H.J., Carter W.B., Edge S.B. et al. (2009). Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 7(2):122-92. 7. Chlebowski R.T., Kuller L.H., Prentice R.L., Stefanick M.L., Manson J.E., Gass M. et al. (2009). Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 360(6):573-87. 8. Breast Cancer: Treatment. (n. d.). Retrieved from http://www.cancerquest.org/breast-cancer-treatment.html. 9. Guidelines for the Management of Breast Cancer. (n. d.). Retrieved from www.emro.who.int/dsaf/dsa697.pdf. 10. Luo B., Cheung H.W., Subramanian A., Sharifnia T. et al. (2008). Highly parallel identification of essential genes in cancer cells. PNAS. 105(51):20380-20385. Read More