Tuesday, September 20, 2011

Men: Beware the ETS Family of Transcription Factors-It May Control Immunity Genes Involved in Prostate Cancer

Cancer is a state of abnormal and uncontrolled cell growth that can potentially spread throughout the body. Cancerous cells have adverse effects, which the body has many defenses against in order to prevent tumor growth and cancer development. The immune system is thought to aid in the suppression or promotion of tumor growth by exerting multiple cellular controls over the death or proliferation of certain cells (Lin and Karin, 2007). With vast numbers of people being affected by cancer on a daily basis, it is important to identify cellular differences between cancerous and healthy states. Identifying changes that might be associated with the onset of cancer proliferation can potentially lead to better understanding of the onsets of cancer.
The prostate, a gland found in males that stores liquid that carries sperm, is highly susceptible to inflammation and cancer (Eisenburg Center, 2005). Prostate cancer is becoming increasingly common in adult males: In fact, in 1990 prostate cancer became the most frequently diagnosed cancer in men, constituting 29% of all cancers found in men (American Cancer Society, 2011). With such alarming numbers of incidence, prostate cancer has become a great health concern of epidemic proportions. However, the theory behind the recent drastic increases may not be solely attributable to an increase in the prevalence of the disease, but instead to new tests, such as the PSA (prostate-specific antigen) test. The PSA test allows for more accurate and determinate prostate cancer detection (Levy, 1995). Even though the higher number of reported cases appears daunting, the PSA test has had the positive effect of detecting the cancer earlier for effective treatment, resulting in decreasing mortality rates. Therefore, PSA tests may allow for prostate cancer to be detected at younger ages, resulting in more healthy, robust men being diagnosed with greater chances of survival with treatment (Hsing, Tsao, and Devesa, 2000).

Even though prostate cancer is becoming increasingly common, it is not an unstoppable force. The body has many preventative responses and defenses, such as the immune system, which is believed to aid in the suppression of cancer development (Lin and Karin, 2007). However, tumors can potentially evade the immune system by either expressing molecules that suppress the immune response or by presenting antigens that are not recognized as foreign by the immune system (Rajarubendra et. al, 2011). If there is a defect in the immune system, or a there is a cancerous cell that can evade detection by the immune system, cancer may proliferate. It is when cancer escapes the mechanisms of tumor suppression that medical attention is needed in order to correct the cellular malfunction and preserve a healthy state.
There are a wide variety of immunity genes that are responsible for the maintenance of the human body. Recently, 37 immunity related genes in prostate cancer have been identified (Shaikhibrahim et. al, 2011). In this study, prostate specimens were obtained from patients with prostate cancer immediately after prostate removal surgery and compared to specimens from normal glands of the patients. The specimens were obtained from a study group that ranged from 45-83 years of age with both moderately progressed and highly progressed prostate cancer. Only high quality RNA samples were used, and laser-capture microscopy was used to isolate RNA from cancerous glands and non-cancerous glands, which were then analyzed using microarray analysis (Shaikhibrahim et. al, 2011). From the experimental data, it was possible to compare the expression of RNA, which is an indicator for the activity of the genes, in both cancerous and non-cancerous cells.
RNA is a direct product of gene activity. Therefore, gene expression differences in cancerous cells and non-cancerous cells could be compared by the amount of RNA obtained from each sample. It was found to be statistically significant if gene expression in cancerous cells had at least ten fold or more difference than genes in non-cancerous cells. This difference in expression of genes in cancerous specimens compared to non-cancerous specimens offers insight into the differences in gene regulation among the two, potentially leading to an understanding as to what conditions support cancer development in the prostate.
The study progressed to not only identify 37 immunity related genes that were expressed differently in cancerous glands, but also to associate the differences in expression with a type of transcription factor. Transcription factors are proteins that are responsible for regulating the production of products from DNA. DNA is the genetic code that is responsible for housing all the detailed information in order to create the proteins necessary for daily life. Transcription factors will attach to DNA and either allow or deny the information to be processed and the products to be produced.
In the study by Shaikhibrahim et. al, a related group of transcription factors, named the ETS family of transcription factors, was found to be responsible for the regulation of expression of 31 of the 37 identified immunity genes that are differently expressed in cancerous glands (2011). Further analysis of these genes found that five of the 37 genes were direct targets of the ETS family members (Shaikhibrahim et. al, 2011). Therefore, the ETS family of transcription factors has a fair amount of control over the production of a large quantity of immunity genes that are abnormally expressed in cancerous prostate cells.
Knowledge of the specific immune genes that can be related to prostate cancer is necessary in order to understand and control prostate cancer. There is an obvious correlation between gene expression and the presence of cancer. The differences in regulation of genes may either be a byproduct of the cancer, or a factor that leads to the ability for cancer to overcome the defenses of the body. In fact, in the study by Shaikhibrahim et. al, it was found that cancers that were more progressed had more abnormal amounts of immunity gene expression (2011), suggesting that gene expression is directly related to the intensity of the cancer.
Prostate cancer is a large contributor to the amount of cancer diagnoses each year and the disease is a widespread problem. Understanding which genes cancer effects will offer insight on what elements may need to be targeted in order to control cancer progression. Manipulating gene control, perhaps on the level of the ETS transcription factors, may help correct the immune defenses against prostate cancer, resulting in greater successes in treatment as well as in prevention.
Shaikhibrahim et. al have laid a foundation for discovering 37 immunity genes that are involved in prostate cancer, and what transcription factor family controls a majority of these important genes. This knowledge of the role of specific immunity genes in cancer would be enhanced by comparisons of gene expression in other types of cancer, such as breast cancer. This would help draw conclusions on whether different immunity genes may be responsible for individual cancer developments. Moreover, if certain types of gene expression can be identified, different mechanisms of accurately detecting presence of cancer in the body may be possible and treatments of manipulating gene expression in order to control cancer development may prove to be an effective cure.
Works Cited:
1. American Cancer Society :: Information and Resources for Cancer: Breast, Colon, Prostate, Lung and Other Forms. "Cancer Facts & Figures 2011." Web. 19 Sept. 2011. .
2. Eisenberg Center at Oregon Health & Science University. Treating Prostate Cancer: A Guide for Men With Localized Prostate Cancer. Comparative Effectiveness Review Summary Guides for Consumers. Rockville (MD): Agency for Healthcare Research and Quality (US); 2005-. PubMed PMID: 21919260.
3. Hsing AW, Tsao L, Devesa SS: International trends and patterns of prostate cancer incidence and mortality. Int J Cancer 85:60-67, 2000.
4. Levy I: Trends in Incidence and mortality of prostate cancer in Canada. Chronic Dis Canada 16:1-11, 2005.
5. Lin WW and Karin M: A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117: 1175-1183, 2007.
6. Rajarubendra N, Lawrentschuk N, Bolton DM, Klotz L and Davis ID: Prostate cancer immunology – an update for Urologists. BJU Int 107: 1046-1051, 2011.
7. Shaikhibrahim Z, Lindstrot A, Ellinger J, Rogenhofer S, Buettner R, Wernert N: Identification of immunity-related genes in prostate cancer and potential role of the ETS family of transcription factors in their regulation. Int J Mol Med. 2011;28(5):799-807, 2011.


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  2. Very interesting. How does the PSA test function compared to the older types of tests?

  3. This was very interesting. I hope thier work encourages other scientists to look for groups of genes involved in transcription factor production and thus regulation of other cancers using similar methods of RNA extraction. I wonder if other cancers also would show comparable amounts of abnormal immune genes.