ArtsAutosBooksBusinessEducationEntertainmentFamilyFashionFoodGamesGenderHealthHolidaysHomeHubPagesPersonal FinancePetsPoliticsReligionSportsTechnologyTravel

Cancer Key Players- Tumor Suppressor Genes and Oncogenes

Updated on November 13, 2013
thebiologyofleah profile image

Leah is a former drug discovery researcher, focused largely on cancer. Due to her background, cancer is major topic of Leah's writing.

Process of Metastasis. Source: Wikimedia Commons, Public Domain.
Process of Metastasis. Source: Wikimedia Commons, Public Domain.

Early cancer researchers long suspected there were two forces allowing for the cancer phenotype- in the 70s and early 80s the working hypothesis was a two-fold concept. Not only were there ‘good’ genes being turned off, but also ‘bad’ genes were being turned on. The idea of ‘good’ and ‘bad’ genes is strictly in the context of the cancer phenotype. The hallmarks of cancer are growth, invasion, and metastasis. These are all normal characteristics in the human body. Cells in various stages of development have these abilities. Growth, of course, is an everyday function of most cells. Invasion or metastasis have a negative connotation- but in the correct context is vital for normal embryonic development as well as the body’s immune function. Cancer seems like an unnatural state but it is ultimately taking components vital to health and manipulating them. One needs to keep in check the damage cancer causes, because on a scientific level it is fascinating.

It is this fundamental idea that all of the abilities of cancer are normal qualities of the body that led these early researchers to conceptualize this two-fold theory. In order for the cancer phenotype to present itself, the cells need to figure out a way to overcome a lot of hurdles. Since so many hurdles were present, these researchers realized a complex pathway leading to cancer involved both turning off certain genes and turning on others. Or in some cases the idea of turning up is a better way to think of it. In normal development certain genes are on but only for a limited time. Others remain on but may produce a product at a lower frequency than the abnormal phenotype requires. The cancer state thrives on being able to constitutively turn on particular genes that would only be on early in life, utilizing them to re-introduce an increased state of growth. In other cases it may be a matter of ramping up a gene’s function to get the desired outcome. The two sets of genes composing the proven theory are tumor-suppressor genes (TSGs) and oncogenes, where the cancer state exists when certain TSGs are shut off and certain oncogenes are turned on or up. Oncogenes are referred to as proto-oncogenes as a precursor stage, when they behave normally and do not contribute to cancer formation.

Combination of turning off TSGs, ultimately the genes are not transcribed, and the turning on (or up-regulating=increased transcription) of oncogenes for cancer phenotype.
Combination of turning off TSGs, ultimately the genes are not transcribed, and the turning on (or up-regulating=increased transcription) of oncogenes for cancer phenotype.

With the general cancer characteristics in mind, it is not a far leap to imagine what variety of functions these two teams provide. Both sets include genes involved with regulating cell division, cell death, cell surface molecules, immune function, and angiogenesis as well involvement in transcription. The cancer cells need to manipulate many different layers of cell function to achieve its primary goal of rapid, uncontrolled cell growth. Then these cells take on the task of invading local tissue first and later may metastasize to other parts of the body. In order to achieve these secondary goals the cells need to alter the cell surface landscape to allow for breaking off from the primary tumor. It may also require new cell surface proteins to invade local and distant tissues. Another critical component for success is angiogenesis, setting up a highway of blood vessels to travel as well to receive factors for continued growth. A somewhat new concept is the idea of avoiding detection by the immune system. This concept will broaden the search for genes involved in cancer to include those with immune function. In order to be successful at these malignant hallmarks, cancer cells need to bypass an intricate system of checks and balances the body possesses to prevent harmful situations.

Cell Cycle and Cyclin-Dependent Kinase (CDK) complexes for control. S=Synthesis, G= Growth, M=Mitosis. Source: Public Domain, wikimedia commons.
Cell Cycle and Cyclin-Dependent Kinase (CDK) complexes for control. S=Synthesis, G= Growth, M=Mitosis. Source: Public Domain, wikimedia commons.

Mitosis is regulated by cell cycle checkpoints, where along each stop of division there are proteins involved in checking the work done to ensure it is correct. If things are not up to par, repair can be done or the apoptosis pathway can be initiated. In the case of apoptosis, programmed cell death, the cells will be disposed of through degradation. This system of checks and balances is just one example of a very complicated system cancer cells need to override in order to achieve a perpetual state of growth. Within the system of cell growth, the DNA repair system, and the apoptosis pathway are other areas cancer cells need to manipulate. Here are three systems all involving many different genes which produce products contributing to checking up on the normal, everyday health of the body. In this example cancer cells need to deactivate the genes which prevent uncontrollable growth, and those that allow for apoptosis. The cancer state doesn’t leave it up to just turning off genes involved in these pathways. This would be like shooting Nerf balls to take down an elephant. At the same time they are turning on genes that help contribute to uncontrollable growth and negatively regulate apoptosis. With these systems in mind, the overall role of both proto-oncogenes and TSGs are considered. Both types of genes have a wide variety of functions in the broad categories of cell cycle regulation, DNA repair, and apoptosis.

BRCA1 chromosomal location. Source: Kuebi, CC BY-SA 3.0, wikimedia commons.
BRCA1 chromosomal location. Source: Kuebi, CC BY-SA 3.0, wikimedia commons.

A few of the most widely known TSGs include Rb, BRCA1, and p53. RB is the gene and Rb protein is its product. Rb functions as a transcriptional repressor and is linked to retinoblastoma. This gene and gene product allowed for many of the pioneer studies done on TSGs as a class and the mechanism of their inactivation in cancer. BRCA1 is the Breast Cancer 1 gene whose gene product is involved in DNA repair damage and is found to regulate other TSGs and proteins that control cell division. The TSG p53 is seen to be mutated in most cancer types. Its normal function is involved in cell damage recognition where the solution is either repair or apoptosis. It achieves this goal by up-regulating the transcription of certain genes as p53 is a transcription factor. Oncogenes are categorized into five groups- growth factors, growth factor receptors, signal transducers, transcription factors, and a fifth group encompassing other functions. An example of an oncogene growth factor is PDGF- platelet- derived growth factor. PDGF, specifically beta, is made from the sis gene. This gene can be constitutively turned on in the cancer cell to ultimately allow for its own uncontrolled growth. A group of signal transducers are the cyclin-dependent kinases (CDKs) which are involved in regulation of the cell cycle. These few examples show only a small area encompassed by these cancer-related genes. TSGs and oncogenes have similar functions all relating to cancer cell progression. The difference between these two classes is that TSGs function to prevent cancer while they are properly functioning and oncogenes function to propel cancer while they are functioning.


The trouble with cancer, of course, is its multi-factorial nature. Technology and advances now allow researchers to pin-point an oncogene active in a particular case of a particular kind of cancer. They can even come up with a drug that shuts down a given oncogene. Unfortunately this doesn’t always mean the end of the cancer. Most times there is something else or many other things contributing to the cancer phenotype. In this article alone it is clear the cancer state tampers with more than one given gene, let alone more than one complex pathway. In addition there are carcinogens, viruses, and other genetic factors all causing and/or contributing to the cancer phenotype. The good news is in some cases shutting down the major oncogene is enough to rid the body of the disease. Regardless of some treatment success, the research continuing to be done on tumor suppressor genes and oncogenes is paramount to our understanding of cancer in general terms but also in specific terms. All of this work can only help lead to more successful cancer treatments in the long run.


Sources

www.news-medical.net/health/Cancer-Pathophysiology.aspx

http://www.ncbi.nlm.nih.gov/books/NBK20806/

Weinberg, Robert A. The Biology of Cancer-First Edition. Garland Science, 2006.

McPhee, Stephen J. Pathophysiology of Disease: An Introduction to Clinical Medicine- Fifth Edition. Lange Medical Books, 2003.

working

This website uses cookies

As a user in the EEA, your approval is needed on a few things. To provide a better website experience, hubpages.com uses cookies (and other similar technologies) and may collect, process, and share personal data. Please choose which areas of our service you consent to our doing so.

For more information on managing or withdrawing consents and how we handle data, visit our Privacy Policy at: https://corp.maven.io/privacy-policy

Show Details
Necessary
HubPages Device IDThis is used to identify particular browsers or devices when the access the service, and is used for security reasons.
LoginThis is necessary to sign in to the HubPages Service.
Google RecaptchaThis is used to prevent bots and spam. (Privacy Policy)
AkismetThis is used to detect comment spam. (Privacy Policy)
HubPages Google AnalyticsThis is used to provide data on traffic to our website, all personally identifyable data is anonymized. (Privacy Policy)
HubPages Traffic PixelThis is used to collect data on traffic to articles and other pages on our site. Unless you are signed in to a HubPages account, all personally identifiable information is anonymized.
Amazon Web ServicesThis is a cloud services platform that we used to host our service. (Privacy Policy)
CloudflareThis is a cloud CDN service that we use to efficiently deliver files required for our service to operate such as javascript, cascading style sheets, images, and videos. (Privacy Policy)
Google Hosted LibrariesJavascript software libraries such as jQuery are loaded at endpoints on the googleapis.com or gstatic.com domains, for performance and efficiency reasons. (Privacy Policy)
Features
Google Custom SearchThis is feature allows you to search the site. (Privacy Policy)
Google MapsSome articles have Google Maps embedded in them. (Privacy Policy)
Google ChartsThis is used to display charts and graphs on articles and the author center. (Privacy Policy)
Google AdSense Host APIThis service allows you to sign up for or associate a Google AdSense account with HubPages, so that you can earn money from ads on your articles. No data is shared unless you engage with this feature. (Privacy Policy)
Google YouTubeSome articles have YouTube videos embedded in them. (Privacy Policy)
VimeoSome articles have Vimeo videos embedded in them. (Privacy Policy)
PaypalThis is used for a registered author who enrolls in the HubPages Earnings program and requests to be paid via PayPal. No data is shared with Paypal unless you engage with this feature. (Privacy Policy)
Facebook LoginYou can use this to streamline signing up for, or signing in to your Hubpages account. No data is shared with Facebook unless you engage with this feature. (Privacy Policy)
MavenThis supports the Maven widget and search functionality. (Privacy Policy)
Marketing
Google AdSenseThis is an ad network. (Privacy Policy)
Google DoubleClickGoogle provides ad serving technology and runs an ad network. (Privacy Policy)
Index ExchangeThis is an ad network. (Privacy Policy)
SovrnThis is an ad network. (Privacy Policy)
Facebook AdsThis is an ad network. (Privacy Policy)
Amazon Unified Ad MarketplaceThis is an ad network. (Privacy Policy)
AppNexusThis is an ad network. (Privacy Policy)
OpenxThis is an ad network. (Privacy Policy)
Rubicon ProjectThis is an ad network. (Privacy Policy)
TripleLiftThis is an ad network. (Privacy Policy)
Say MediaWe partner with Say Media to deliver ad campaigns on our sites. (Privacy Policy)
Remarketing PixelsWe may use remarketing pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to advertise the HubPages Service to people that have visited our sites.
Conversion Tracking PixelsWe may use conversion tracking pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to identify when an advertisement has successfully resulted in the desired action, such as signing up for the HubPages Service or publishing an article on the HubPages Service.
Statistics
Author Google AnalyticsThis is used to provide traffic data and reports to the authors of articles on the HubPages Service. (Privacy Policy)
ComscoreComScore is a media measurement and analytics company providing marketing data and analytics to enterprises, media and advertising agencies, and publishers. Non-consent will result in ComScore only processing obfuscated personal data. (Privacy Policy)
Amazon Tracking PixelSome articles display amazon products as part of the Amazon Affiliate program, this pixel provides traffic statistics for those products (Privacy Policy)
ClickscoThis is a data management platform studying reader behavior (Privacy Policy)