What Changes in Cells and DNA Lead to Cancer - Essay Example

The Cellular Basis of Cancer: What Changes In Cells and DNA Lead to Cancer, and How Do These Changes Affect The Cell Cycle? Name: Unit: Course: Submission Date: Professor name: Introduction to cancer biology Cancer terminology refers to a multitude of conditions with uncontrolled and unscheduled cellular proliferation characteristics. In biology, many homeostatic processes revolve in competitive interactions. The secretion of paracrine and autocrine factors important in preventing neighboring cells from anomalous growth, subsequently resulting into normal metabolism and healthy development is regulated by normal epithelial cells. Tumor initiation is said to be triggered by this homeostatic cell competitive structure (Kosaka et al., 2012, p. 1397). Cancer arises from a multistep-process in which intense behavioral and metabolic changes occurs within the cell, triggering untimely and excessive growth so that they elude the immune system keeping watch, and thus attack tissues far off forming metastasis (Mechanisms of Carcinogenic, 2008 p192). This essay will critically explore existing literature and answer the question, “the cellular basis of cancer: what changes in cells and DNA lead to cancer, and how do these changes affect the cell cycle?” Cell growth and cancer initiation overview In understanding cell growth via Drosophila experiment, there is evident competition between normal cells in comparison to the transformed cells to ensure survival a process referred to as cell competition. When stress hits some group of cells, it breaks down to cells-subpopulations with differing damage degrees. If the conditions are noncompetitive severe damaged cells die after a short while, but cells suffering from moderate damage may survive to another generation. This is a red flag of a negative phenotype transduction. Slightly destroyed cells in competitive conditions are easily ruled out from the cell group as the winners; ‘healthy cells’ send death signals to losers; ‘damaged cells’ at the same time, damaged cells sends growth indicators to the healthy cells. This feed-forward process gives a room to the cell production to eradicate losers (abnormal cells) and ensure normal cells are maintained in a limited space (Kosaka et al., 2012, p. 1397). Throughout human lifespan, spontaneously forming mutations form in somatic cells. Most of these mutation have no noticeable effects, while others may alter fundamental cellular functions. Mutations that occur in multicellular organisms’ due to DNA replication errors in somatic cells and germline cell lead to cancer and genetic diseases respectively. Replication errors within human tumors also increases chances of tumor heterogeneity and mutate phenotype (Mertz, Harcy, & Roberts, 2017 p1). Somatic mutations occurring early in life may result to developmental disorders while mutations accumulating overtime during lifespan may result to cancer development and fasten aging (Matincorena & Campbell, 2015 p.1483). The characteristic forming oncogenesis is that metabolic and genetic changes reprogram living cells such that they exhibit uncontrolled growth. This means that viable abnormal cells for elimination may survive and form an expansion-backwards cell competitive regulation, subsequently forming a tumor mass that does not need special signals to catalyze cell division and growth. As the losers cells grow they form new features like new enzymes production, decreased cell adhesion, and structure changes. These changes can be inherited and allow the cell progeny and itself to grow and divide amidst normal cells that may prevent the nearby cells growth. Thus, a tumor process involves a tumor-suppressive gene (p53) between the progenitor cells and the hematopoietic stem cells. This shows that p53 gene alteration may cause turbulence within the homeostatic mechanism and result into tumor initiation. Possibly, p53 target genes might results from intercellular communication relationship between losers and winners (Kosaka et al., 2012, p. 1397). Cancer controls failure during cell division Gene malfunction About 35,000 genes in the genome of human beings is linked with cancer development. When these same genes are altered they result into different types of cancers. These gene malfunctions can be categorized into three broad groups, tumor suppressors, that synthesizes proteins that bars cell division or triggers cell death; proto-oncogenes producing products of proteins that inhibit normal death of a cell or promotes cell division; third group houses DNA repair genes that blocks cell mutations which result into cancer. Tumor suppressor and proto-oncogenes work like car’s brakes and accelerators respectively to ensure controlled growth. However, tumor suppressors affecting mutations deters the normal growth inhibitions while mutations producing oncogenes (types of proliferation causing cancer or mutated genes) speeds up growth. This is so because, proto-oncogenes converting mutations to form oncogenes catalysis the encoded protein activity or the normal gene expression. These forms of mutations gain-of-function or dominant mutation and therefore a single mutated gene can promote cancer, (Hyland, n.d., p81). Cancer and cell cycle Tumorigenesis brings in functions that evade therapy and immune surveillance, disable modalities of cell death, and promote cell growth unlike in normal cells. The growth and division of the normal cells follows the cell cycle (Jin, et al., 2007 p. 379). However, mutations in tumor suppressor and in proto-oncogenes gives room for abnormal cell growth against the cell cycle normal controls. The cell houses various proteins that man the cell cycle events and timing, ensuring tight regulation guaranteeing that cells division occurs when needed. The cornerstone of cancer development is losing this regulation. Cyclin-dependent kinases is the cell cycles major control switches. For every cyclin-dependent kinase a complex protein, cyclin enzyme attaches itself and activates the process of cyclin-dependent kinase. Within the complex cycle, the kinase enzyme adds to various proteins a phosphate to necessitate progression of the cell during the cycle. These phosphate added may change the protein structure and either inactivate or activate the protein in reference to its function. Various cyclin-dependent cyclin complexes/kinases occur (checkpoints) at growth phase, synthesis and mitosis entry point, and also additional factors that promote cell preparation to enter mitosis (M) and synthesis (S) phase, see figure 1 (Collins, Jacks & Pavletich, 1997 p. 2776). DNA damage checkpoints form fundamental control points within the cell cycle promoting damage repair. Checkpoint functions loss results into genomic integrity loss and genetic damage accumulation promotion within the daughter cells. Deficiency in checkpoint leads to DNA aberrations (Nojima, 2004 p3). Within the cell cycle one important protein is transcription factor, p53 that attaches itself to DNA triggering p21 protein transcription. P21 acts as a barrier against cyclin-dependent kinase activity needed to steer the process through guiescence (G0) phase 1. In case the DNA damage is vast beyond repair the cell is activated to commit suicide by the p53. In case there is an abnormal cell division, or DNA damage in normal cells dies and stop division. For cancer cells the division and growth continues regardless of the presence of damaged DNA or in presence of abnormal cells. These progeny cells of the cancer carries abnormal DNA necessitating accumulation of more damaged DNA with the cell division progression (National Cancer Institute, 2010 p.5). Figure 1: Cell cycle in a mammal. During each cell cycle division, there is a single chromosome replication (S-phase or DNA synthesis) and segregated to form two identical daughter cell in gene (M-phase or mitosis). G1 and G2 gives growth and reorganization intervals. Quiescence (G0) means end of division. CDK-cyclin complexes regulated the cycle progress (Collins, Jacks and Pavletich, 1997 p.2776) Tumor suppressor genes Tumor suppressor genes proteins work by preventing tumor formation and cell growth in a normal cell. In mutant genes, these cells do not have the capacity to ensure normal inhibition of division and growth of the cells. Tumor suppressor gene products mostly act in the nucleus, cytoplasm and the cell membrane. When these genes are mutated they result into recessives to cell growth inhibition. Therefore, unless the two copies of a normal genes are mutated the traits of uncontrolled growth remains unexpressed (Bethseda , 2007). DNA repair genes In a normal cell, various factors repair damages within the chromosomes preventing or reducing the chances of cell mutations. With a mutated DNA repair gene no more production of its products. This bars DNA repair process and trigger more mutations to build within the cell. These mutations are known to increase cancerous frequency changes in a cell. For example, XP (Xeroderma pigmentation) is a DNA repair gene. A defect predisposes UV light sensitive individuals to more than 1000 chances of developing all forms of skin cancer (Rediscoverying Biology, n.d. p5). Signal transduction and oncogenes Proto-oncogenes code in protein in normal cells signals the nucleus to initiate cell division. The signaling proteins work on a series manner referred to as a signal transduction pathway or cascade. The pathways includes intermediary proteins that transport the signal via the cytoplasm, the signal molecule; a membrane receptor and transcription factors within nucleus which triggers the cell division genes. Within the cascade, in each step protein or one factor activates the next. But, in some cases some factors in a cell may trigger more than a single factor. The alteration of proto-oncogenes process is oncogenes. With oncogene the cascade signaling is continuously activated leading to an increased production of growth stimulating factors. For example, proto-oncogene MYC codes a transcription factor. MYC mutations may form oncogene linked with 70% of occurring cancers. Proto-oncogene RAS is an “on-off” switch within the signal cascade. When mutations occurs on RAS the signaling pathway remains “on” resulting into a controlled growth of the cell. RAS contributes to about 30% of commonly occurring cancers. A proto-oncogene conversion to an oncogene is likely to arise because of the increase of the normal proto-oncogene number of copies, genes rearrangement within the chromosomes relocating the proto-oncogene to another location and proto-oncogene mutation (Rediscoverying Biology, n.d. p4). Tumor clonality Tumor clonality is a common feature in cancer. This is where tumors development from one cell start abnormal proliferation. X-chromosome analysis has been a pointer of the single-cell origin. X activation is random during embryonic development, with one X chromosome in some cells left inactivated, while in other cells the inactivation of the other X chromosome occurs. Therefore, in case a female has heterogenous X chromosome gene, different cells will have an expression of different alleles. With normal tissues different inactive X-chromosomes occurs in a mixed up manner hence both alleles expression is detected in heterozygous females in normal tissues. However, for tumor tissues, in a heterozygous gene; in X chromosome only one allele is expressed. This implies that all tumor forming cells had a single cell origin, where X inactivation pattern was fixed prior to the tumor initiation process. Cancer cells form via a multistep process where gradually cells become malignant via a progressive alterations series. This is so as most cancer come later in life (Sunderland & Cooper, 2000 no pg). Characteristics off normal cells versus cancer cells To ensure viable division, normal cells needs external motivating growth factors. Cell division stops in case, the regulation of these growth factors synthesis is impaired via normal regulation. With cancer cells growth continues with or without the presence of these factors as the cells lack positive growth desire. Therefore, these cells behave with anomalies as independent cells rather than like the tissue share. Contact inhibition is evident with normal cells because cell division ceases when they come into contact with other cells. Normal cells can only divide to fill a gap and stop when the gap is filled. However, with cancer cells such characteristic is absent and even when no room for growth they will continue growing resulting to a formation of a large mass inform of cells. When normal cells die (apoptosis) they are orderly replaced by new cells in a controlled manner. At maximum, normal cells divide fifty times prior to their death. This is in line with their DNA replication capacity for a few times. On replicating the chromosome telomeres (ends) shorten. The enzyme telomerase in growing cells replaces these lost ends. For an adult, cells telomerase is absent in cells thus, the number of cell division is limited, but, with cancer cells, telomerase is activated promoting unlimited cell divisions events (Rediscoverying Biology, n.d. p6). Cancer cells have differing metabolic properties in relation to normal cells. They can undergo glycolysis both aerobically and anaerobically. Thus, for cancer cell mitochondria function is aggravated to produce more ATP compared to normal cell (Mikirova, 2015 pXX). With normal cells, scientist finds it difficult to grow them within the laboratory set-up. Normal cells are highly sensitive to the conditions of cell culture and require specialized media and treatments. Further, normal cell divide limited manner and then stops. With tumor cells doing culture is simple, divide indefinitely and proliferate within the lab easily (EDVOTEK, 2015 p6). Looking into the physical characteristics, due to changes with cancer cells the nuclear structure is irregularly and large in shape with alterations on the chromosomes with the morphological characteristics being the primary diagnosis of presence of cancer. Normal cell on the other hand have ellipsoid and regular shape with cancer cells being contoured and irregular. With cancer cells there is nuclear lamina proteins structural changes, which offer cell mechanical support, and such may alter gene expression or affect chromatin organization. Also, the cell structures feature changes is evident with cell cancers. For instance, the peroxisomes increases in number, there is underdevelopment within the Golgi apparatus, mitochondria and the endoplasmic reticulum often decreases. Why uncontrolled cancer cell growth? In conclusion, cancer cells from the above research shows they have faster growth. In summative form this arises because cancer cells use and recruit normal cells selfishly to promote their survival and proliferation. The uncontrolled growth can be explained using the 6 hallmarks: metastasis and invasion activation (having spread ability to other sites); angiogenesis (growth of new blood vessel stimulation abilities); apoptosis (ability to resist cell death); override ‘Stop’ signals (tumor-suppressor genes anti-growth signals-not waiting for ‘Go’ indicator) and Immortality (limitless replication and continuous cell division) (Hejmadi, 2010 p14) see Figure 2. Figure 2: Cancer Hallmark, Hanahan & Weinberg, (2011) References Bethseda, MD. 2007. Understanding Cancer. Accessed [Online]. https://www.ncbi.nlm.nih.gov/books/NBK20362/, 4/26/17. Collins, K., Jacks, T. & Pavletich, N.P. 1997. The cell cycle and cancer. PNAS, Vol. 94, No. 7, pp 2776-2778. EDVOTEK, 2015. Edvo-Kit #990: Morphology of Cancer Cells. EDVOTEK, Inc. Hanahan, D. & Weinberg, RA. 2011. Hallamarks of cancer: the next generation. Cell, vol. 144, Issue 5, pp 646-674. Hejmadi, M. 2010. Introduction to Cancer Biology, 2nd edition. ISBN 978-87-7681-478-6. Hyland, KM. n.d. Tumor Suppressor Genes and Oncogenes: Genes That Prevent and Cause Cancer (Biochemistry/ Molecular Biology Lecture. Accessed [Online]. http://biochemistry2.ucsf.edu/programs/ptf/m3%20links/TumorSuppressLEC.pdf, 4/27/17. Jin, S., SiPaola, RS., Mathew, R. et al., 2007. Metabolic catastrophe as a means to cancer cell death. Journal of Cell Science, No. 120, pp. 379-383. Kosaka, N., Iguchi, H., Yoshioka, Y. et al., 2012. Competitive interactions of cancer cells and normal cells via secretory MicroRNAs. The Journal of Biological Chemistry, Vol. 287, No. 2, pp. 1397-1405. Martincorena, I. & Campbell, PJ. 2015. Somatic mutation in cancer and normal cells. In Science, Vol. 349, No. 6255, pp. 1483-1489. Mechanisms of carcinogenesis 3, 2008. Molecular Hallmarks of Cancer. Accessed [Online]. https://www.iarc.fr/en/publications/pdfs-online/wcr/2008/wcr_2008_5.pdf, 4/26/17. Mertz, TM., Harcy, V. & Roberts, SA. 2017. Risks at the DNA replication fork: effects upon carcinogenesis and tumor heterogeneity. Genes, Vol. 8, No. 46, pp. 1-21. Mikirova, NA. 2015. Bioenergetics of human cancer cells and normal cells during proliferation and differentiation. British Journal of Medicine and Medical Research, Vol., 7, No. 12, PP XX-XX. National Cancer Institute, 2010. What You Need To Know about Melanoma and Other Skin Cancer. National Institute of Health. Nojima, H. 2004. G1 and S-phase checkpoints, chromosome instability and cancer. Methods Mol Biol, No. 280, pp.3-49. Redicsoverying Biology, n.d. Cell Biology and Cancer. Accessed [Online] https://www.learner.org/courses/biology/support/8_cancer.pdf, 4/26/17. Sunderland, MA. & Cooper, GM. 2000. The cell: a Molecular Approach, 2nd edition. 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