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Identification of Oncogenes in Breast Cancer Development Crimson Publishers Wings to the Research Review Article Identification of Oncogenes in Breast Cancer Development Pranav Rajashekar1, Chikezie OMadu2 and Yi Lu3* 1Departments of Biology and Advanced Placement Biology, White Station High School, Memphis, Tennessee 28117, USA, [email protected] 2Departments of Biology and Advanced Placement Biology, White Station High School, Memphis, Tennessee 28117, USA, [email protected] ISSN: 2637-773X 3Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA, [email protected] Abstract The role genes play in cancer progression and cancer subtypes has gained interest in research over the years. Numerous studies have focused on the potential proliferation of oncogenes and their transformation from proto-oncogenes. Through various research, these components have led to unique cases of cancer. Oncogenic occurrences are being studied to limit their influences on future generations, oncogenesas their relation discussed to the in thisincreasing paper are rates sectioned of specific into cancerthree groups types basedhas not on gone the effects unnoticed. of their The mutations, focus of andthis thesewill be three on the groups effects are of tyrosine-kinase oncogenes and activity,proto-oncogenes transcription in breast factors, cancer and GTPasedevelopment. activity. The Moreover, specific the study of these oncogenes can reveal a novel understanding of breast cancer, which can then be applied to develop treatments. *Corresponding author: Yi Lu,Department Keywords: Oncogene;Proto-oncogene;Tyrosine-kinase activity;Transcription factors; GTPase activity of Pathology and Laboratory Medicine, University of Tennessee Health Science Introduction Center, Cancer Research Building, 19 South Manassas Street, Memphis, TN With the growing prevalence of breast cancer cases, the role of oncogenic factors has been 38163, USA, Email: [email protected] demonstrated in many studies. Recently, despite the number of breast cancer cases continuing to increase, growth in the number of cases has slowed down [1]. Studies have consistently Submission: : September 29, 2020 shown a relationship between oncogenes and the presence of breast cancer. Numerous Published: October 28, 2020 oncogenes are related to the proliferation of cells during the stages of breast cancer. These are originally mutated and directly lead to negative effects by inducing overproduction of cells in Volume 5 - Issue 3 the body [2]. The deregulation of such genes has been noticed in various cases of breast cancer. How to cite this article: Pranav Alterations to these genes can cause deformed mechanisms in various cellular functions, such Rajashekar, Chikezie OMadu, Yi Lu. as cell division and growth, and can impede the victim’s survival chances [2]. Although there are still many unknowns regarding oncogenes, research is being conducted to understand Cancer Development. Nov Appro in oncogenes’ potential effects on cancer-inducing pathways [1]. Novel understanding regarding CanIdentification Study. 5(3). of OncogenesNACS.000612. in Breast2020. DOI: 10.31031/NACS.2020.05.000612 the role of oncogenes in breast cancer development as derived from this research is then being used in developing treatments [1]. This paper will focus on certain oncogenes that have Copyright@ Yi Lu, This article is facilitated breast cancer development through the alteration of tyrosine-kinase activities, distributed under the terms of the Creative transcription factors, and GTPase activities. Recent advances in breast cancer development Commons Attribution 4.0 International License, which permits unrestricted use and treatment will also be discussed [3-6]. and redistribution provided that the original author and source are credited. Tyrosine Kinase-Affecting Breast Cancer Oncogenes As part of the Epidermal Growth Factor Receptor (EGFR) family, the EGFR gene, also commonly known as ErbB1, codes for the EGFR and is located on chromosome-7 [7-9]. EGFR regulates certain cellular processes, such as cell growth and proliferation. It does so through a receptor tyrosine pathway, a pathway in which the receptor is dimerized then phosphorylated other receptors. This occasionally creates a heterodimer group [9]. In the following events, [9]. Specifically, the binding of ligands to the receptors induces the dimerization of EGFR with the cytoplasmic component of the receptor undergoes a structural change, which allows for phosphorylation when the tyrosine kinase pathway is induced [8]. For accurate cellular Novel Approaches in Cancer Study 492 NACS.000612. 5(3).2020 493 growth regulation throughout the cell cycle, numerous biological causing the cell cycle to progress at increased rates [3,5]. This pathways depend on this Receptor Kinase Pathway (RTK) to be increase leads to a proliferation of cells, which then develop into induced through mediums like the EGFR proto-oncogene. However, tumors responsible for breast cancer [10-12]. mutations can act onto these proto-oncogenes and turn them into cellular growth and tumorigenesis in humans, as it codes for a the gene leads to the overexpression of the EGFR genes, causing Another proto-oncogene, called the SRC gene, influences oncogenes that promote tumorigenesis. The amplified version of an increase in the number of EGFR within the cell [8]. Elevated cancer. Prominently used in cell signaling, the SRC gene can lead to amounts of EGFR can then cause an increase in the induction of nonreceptor tyrosine kinase that influences the induction of breast further growth and expansion in human cells if not regulated. The genes throughout the cell. The Ras protein can also come into play SRC gene consists of Tyr416 and Tyr527, which are both respective through the tyrosine kinase process, which causes an increase for autophosphorylation-promoting and phosphorylation- in cell proliferation [8]. Also, the tyrosine kinase process plays a inhibiting sites [13]. Furthermore, it contains an SH3 domain, SH2 role in the transition from the G1 and S phases of the cell cycle, domain, tyrosine kinase site, and a C-terminal regulatory site [13]. critical for cell survival and growth [8]. The erbB2 gene’s location In numerous people with breast cancer, an increase in the SRC is along chromosome-17, and it functions as a transmembrane gene expression and SRC Family Kinases (SFK) activity is present. tyrosine receptor [4]. In addition to this, the erbB2 gene can The levels of SFK or SRC family kinases are relatively higher in encode a product that can act as a transmembrane glycoprotein, tumorigenesis-inducing tissues than normal tissues in mammals which allows for the emergence of the EGFR family [3]. This family [10]. Studies show that the dephosphorylation of the location consists of four receptors, where the ErbB2 is primarily targeted as Tyr530 on the SRC gene could have led to these increased kinase activity levels and normal levels of SRC proteins [10]. SFK induction [6]. The overexpression of the gene can cause the ErbB2 receptor the preferred binding site since it lacks ligand binding specificity to increase in cells drastically, and growth factor stimuli can be to cell proliferation, growth, and survival [10,12]. If the SFK activity reached to give rise to malignant tumors [3]. The erbB2 gene is could lead to cancer because specific SFKs amplify signals that lead increases in the cell exceeding that of normal cells, increased found to be overexpressed in approximately 30% of breast cancer tumorigenic rates can be induced in breast cancer patients. Furthermore, the effects of SFK can carry over to phosphorylating known as the HER2 gene, the erbB2 oncogene codes for a receptor cases, making it a significant cause for the malignancy [4]. Also Receptor Tyrosine Kinases (RTKs) at numerous Tyr-like locations, that always has an open structure, further making the receptor the and this can change their signaling mechanisms and product over primary target of ligands. Overexpression of the HER2 gene causes time [11,12]. In certain mice with the HER2 gene, the activation and the HER2 receptors to increase throughout the cell, which results induction of the SRC gene correlated with the tumorigenesis in the in an expanding rate of cell growth and multiplication. After the mice, which leaned toward the potential dependence of SRC genes dimerization process that accompanies such tyrosine receptors, on the EGFR family during the progression of breast cancer risks in the termination of a cell cycle inhibitor called p27Kip1 is induced, mammals [11]. Figure 1:The MYC-MAX complex that binds to the E-Box. Triggered by the MYC gene’s overexpression, other transcription factors are overregulated in response, as they are usually regulated by homeostasis. The results lead to cellular growth (adapted from [61]). Nov Appro in Can Study Copyright © Yi Lu NACS.000612. 5(3).2020 494 Transcription Factor-Affecting Breast Cancer Oncogenes location within the sequence vary, hinting that certain signaling mechanisms are used to activate genes through p53 mediums [21]. By binding to these various sites on target genes, p53 can facilitate prominent role in breast cancer development. The proto-oncogene Identified thirty years ago, the c-MYC gene continues to play a the transcription of proteins that regulate mechanisms needed is regulated for normal cellular maturity, cellular proliferation, and for cell survival. For instance, Puma and Hdm2 are examples of is essential for continuing the cell cycle [14-16]. Since the c-MYC proteins
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