Good Cholesterol and Breast Cancer Risk - Essay Example

?Gender, Science and Technology Primary science article and Popular article – Summaries The primary science article, Scavenger receptor B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development, written by Christiane Danilo, Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P Lisanti and Philippe G Frank, explains the role of Scavenger receptor Class B Type I (SR-BI) in breast cancer development. Many medical researches have proved that cholesterol accelerates and enhances tumor formation, and cholesterol is an important regulator particularly in the development of breast cancer. High Density Lipoprotein (HDL) and its cellular receptor, Scavenger receptor Class B Type I help in scavenging and removing LDL or "bad" cholesterol  from peripheral tissues of the cells. This phenomenon reduces the risk of heart diseases but at the same time HDL also stimulates migration and activates signal transduction pathways in the human breast cancer cell lines, thus acting like a catalyst in the development of breast cancer. Thus knocking down the HDL receptor, SR-BI by some pharmacological methodologies play an essential role in regulating cellular proliferation and migration, thus controlling the growth of tumor cells, and hence SR-BI can be essentially used in the treatment of breast cancer in humans. The Popular article, Good cholesterol and breast cancer risk explains about the above detailed primary research article in a crisp manner. Though HDL that is, good cholesterol is good for health and acts like a protective shield against heart disorders, it has a negative impact on breast cancer development in humans. Higher the level of HDL in blood, higher is the risk of developing breast cancer. Thus limiting the HDL receptor, SR-BI the rapid proliferation of tumor cells were found to be greatly reduced. The popular article also interacts with Dr. Philippe Frank, head of the research team and a cancer biologist in the Department of Biochemistry and Molecular Biology at Thomas Jefferson University who stresses on the importance of inventing more specific drugs to inhibit SR- BI and the safer level of HDL to be mentioned in cancer patients. How it relates to the theme – ‘Gender, Science and Technology’ Both the articles are interlinked and have a strong correlation with the theme of ‘Gender, Science and Technology’. The main focus of both the articles is about the treatment for breast cancer. Though the exact cause for breast cancer is still a topic under research, analysing the risk factors can show who is most likely to develop the disease. Lifestyle choices, genetic disorders and medications taken for some kind of diseases may be some of the risk factors for developing the disease but some risk factors are more vulnerable, particularly one’s ‘Gender’. Breast cancer is most common in women because they have more breast tissue than men. Breast cancer causes include what stimulates the breast tissue to grow and develop. Female relatives can also be a risk factor for getting breast cancer. If one’s mother, sister or daughter have breast cancer, the chances of getting the disease is doubled. Though cancer of several types is the leading cause of death in the world, medical science and technology has empowered people to make life changing decisions by matching them with modern and advanced treatment options based on individual conditions of the patients. Modern science and technology has revolutionized the breast cancer research therapies and now chances of overcoming breast cancer are much better than in earlier days. Main Scientific Claim The authors claim that their examination about the role of HDL and SR-BI in the regulation of cellular signalling pathways in breast cancer cell lines and development of tumors show that, HDL can stimulate the signal transduction pathways in the human breast cancer cell lines. Then, accelerate the formation of tumors and hence knocking down of HDL receptor, SR-BI limits the above HDL induced activation of cancer progression. Based on their detailed analysis they also claim that regulation of SR-BI function, can limit tumor development. Results to support the Claims The authors have achieved three important results in order to support their claim. These results are explained in detail in the primary science article but not in the popular article. Result 1: Role of HDL3 in cell migration First, they have proved that HDL3 stimulates migration and activates the signalling pathways’ mitogen –activated protein kynase’ (MAPK) and phosphatidylinositol 3- kinase (PI3K) in the two breast cancer cell lines, MDA-MB-231 and MCF7. Cell migration is the first step in the development of tumors. To study the effect of HDL on cancer cell migration, the authors used HDL3 as a chemoattractant (a substance which attracts motile cells of a particular type) on MCF7 and MDA-MB-231 cells. They found that HDL3 induced migration by activating Erk1/2 (extracellular-signal-regulated kinase 1 and 2) and protein kinase AKT which are the growth stimulating factors in both the cancer cell lines to a greater extent when compared to the results in which controls (CTL) used as a chemoattactant.(Figure 1) Result 2: Effects of Knocking down the HDL receptors Second, limiting selectively the HDL cholesterol uptake by inhibiting SR-BI proved the cutting down of the above cell signalling activities induced by HDL. In order to down regulate the HDL receptor, SR-BI the MDA-MB-231 and MCF7 cells were stably transduced by lentiviral particles containing shRNA sequences specific for SR-BI (shSRBI). Cells were incubated with 100µg/ml HDL. Knockdown of SR-BI was analysed by western blot analysis. The results proved that inhibiting SR-BI in the two human breast cancer cell lines cut downs the signalling through AKT and MAPK pathways. Further to study the effect of downregulating SR-BI on cellular cholesterol homeostastis, cholesterol content of shCTL and shSR-BI was quantified. The shSR-BI MDA-MB-231 cells contained significantly lesser total cholesterol content compared to shCTL MDA-MB-231 cells. They also proved proliferation and cellular migration was greatly reduced in sh-SRBI MDA-MB-231 cells. Result 3: Decreased proliferation and tumor growth. Third, inhibiting SR-BI using the drug BLT-1 resulted in decreased proliferation, migration and tumour growth in the breast cancer cell lines. To study the effects of SR-BI knockdown in vivo that is in a living organism shSR-BI and shCTL MDA-MB-231 cells were injected into mice and four weeks after injection tumors were excised from dead mice. Tumor mass and volume was measured. Tumors obtained with shCTL MDA-MB-231 were significantly larger than those obtained from shSR-BI MDA-MB-231. (Figure 6). Further immunohistochemistry analyses showed the reduction in Sr-BI protein expression in ShSRBI MDA-MB-231 – derived tumors compared with ShCTL MDA-MB231. Similar results were obtained for MCF7 cells also. All the above results are elaborately explained in the primary science article where as the popular article just proposes in brief how higher levels of HDL in blood can cause the development of breast cancer and how limiting the expression of HDL receptor SR-BI in the cells with the help of a drug BLT- 1 controls the proliferation of cancer cells. In-depth technical details of the of the research and its results are not stated in the popular article but still going through the article can give an overall idea about the entire research process. Figure No.6 – Important figure of the article The figure which can be considered as the important figure of the article, is the Figure 6 titled, Knockdown of SR-BI inhibits xenograft tumor growth in vivo. Coming in the last part of the article, this figure aptly sums and also concludes what the scientists are trying to prove and validate. That is, the key result of the entire research is based on how knocking down the HDL receptor, SR-BI. This figure shows how it was knocked down resulting in reduced tumor growth in a mouse xenograft model, and hence applying the phenomenon in treating breast cancer. This result is illustrated with the help of Figure 6, the most important result of the primary science article, thus making it the key figure of the article. Alternative Explanations When one goes the research article, it is clear although the scientists used outside studies and theories, maximally it was to back up what they are saying. In that direction, there is not much of alternative explanations and as those studies back the scientists’ claims, it does not make more sense. In addition, it helps in understanding the study in a more clear manner, and with explanation of key technical process, it makes a better read. For example, xenograft means transplanting tissues from a donor of one species to an acceptor of different species. In this research the two breast cancer cell lines MDA-MB-231 and MCF7 of human containing two different types of RNAs shCTL and ShSRBI are injected into the flanks of mice for the purpose of research. RNA (Ribonucleicacid) acts like a messenger carrying the instructions from DNA for protein synthesis, and that helps in knocking down SR-BI. The two breast cancer cell lines MDA-MB-231 and MCF7 modified with these two types of RNAs (shSRBI and shCTL) were injected into athymic nude mice and four weeks later these mice were killed and tumors were excised. Tumor volume and mass were examined, which are the variables taken into consideration along the columns in figures 6A and 6B. Inferring the above figures it is so evident that the tumors obtained with shCTL cancer cell lines were significantly larger than shSRBI cancer cell lines. Similar results were obtained while examining the tumor mass also. Further Western blotting also called as immunoblotting was done. Immunoblotting is a technique used for analysis of individual proteins in a protein mixture. The denser patterns indicate high proliferation of cells in shCTL MDA-MB-231 cells when compared to shSRBI MDA-231 cells which ascertains the claim that cells with fewer SR-BI receptors display reduced proliferation rates and migratory abilities than cells with normal SR-BI levels. Thus these results show that by regulating SR-BI, breast cancer can be treated effectively. The Questions Unanswered 1) It is a well known fact that HDL protects against the risk of heart diseases. The research claims the blocking of HDL receptors to treat breast cancer. But what may be the consequences and side effects of blocking HDL receptors as they play a vital role in removing excess cholesterol from blood circulation? Does it mean indirectly the potential risk of heart diseases get increased? As the popular article states “what's good for one disease may not be good for another” in the sense High levels of HDL are interlinked with breast cancer, we should also have in mind the fact that  people who have low HDL cholesterol will have greater risk of developing heart disease than people with high HDL levels. This is an alarming fact which cannot be ignored. 2) In the methodologies suggested in the research article it is mentioned that human plasma samples were obtained from adult female volunteers. Though male breast cancer is rare still there are occurrences of male breast cancer. Why not the samples collected from males. Will the research end up with same results for samples from both genders? Getting older, high estrogen levels, being overweight, usage of alcohol, taking hormonal medicines are some of the risk factors for male breast cancer. Any research must focus on the wellbeing of all humans irrespective of the gender and the results obtained must also be unbiased to any gender. 3) According to the research SR-BI receptor will be blocked with the help of the drug BLT-1. Is that the only drug available for this purpose? If so what are its other side effects in human? Whatever may be treatment for cancer, chemotherapy, biological therapies, hormone therapies, bisphosphonates or use of painkillers have their own side effects. So whatever may be the drug proposed as a result of any cancer research, we must carefully consider the side effects of the drug because the goal of any research is to benefit mankind without harming them. Underlying assumptions Among the various types of cancer that afflict humans, breast cancer that primarily affects women is one of the key types, as it not only affects woman’s physical health but also her psychological fortitude. With women throughout the world suffering from this affliction in higher numbers particularly in the recent past, it has started to evolve into a major public health issue. On the positive side, advanced treatment options as well as effective drugs that are available for breast cancer, are saving the lives of many women, thereby helping them to live a normal life or even a semblance of normal life albeit with minor ‘alterations’. Thus, with breast cancer becoming a major health threat, the very first line of the research article states that > 200,000 women in United States were affected by breast cancer in 2012. Here the authors have not much considered the fact that breast cancer can also affect males and have assumed that only women are the victims of breast cancer. Certain number of men has the possibility of suffering from Gynecomastia, which is due to the increase in the amount of breast tissue in the men and that leads to growth of breast in men. Even if it is of minimum size, there are chances of breast cancer affecting those breasts in men. They have also estimated that, in United states 40,000 women die due to breast cancer. This clearly proves that they have limited their studies to the region of United States. This underlies the common assumption that, white women are slightly more likely to get breast cancer than African-American women. African-American women, still are more likely to die of breast cancer and also Asian and Native-American women have a lower risk of getting and dying from breast cancer. Apart from the race related and ethnic related factors, there are many more risk factors, and the authors limit their scope by not focusing those factors in detail. Of the key risk factors, age, family history, child bearing, menopause, etc., can also have an impact in the cause of breast cancer. Various studies have found that women of age greater than 50 are prone to more risk than the women of age 40. (Taghian, Smith and Erban, 2009). The women, who have never given birth to a child, face far more risks at the time of menopause. On the same lines, hormonal replacement therapy is also seen to be another reason for the breast cancer. The glandular tissue of the women are replaced by the fat during menopause time, when hormone therapy is done for these patients, they are more prone for the breast cancer. (Taghian, Smith and Erban, 2009). However, as mentioned above, these factors were not focused in a detailed manner, thereby limiting the scope. The increase in age is one of the most important factors that increase the risk. They have proposed their research results assuming cholesterol as the key regulator of breast cancer development. They have not considered other dietary issues leading to breast cancer development because many studies going on regarding the role of particular foods in the cause of breast cancer. Also in their work they have dealt with HDL assuming only its harmful effects with least consideration for the very essential function of HDL. That is, HDL play a very important role in the is removal of excess bad cholesterol from blood stream and transporting it to the liver for its excretion, which is one of the key functions that needs to carried out aptly. So what level of HDL is safe for the human cells is very important question which is left unanswered in the primary science article. Thus, it is clear that certain assumptions relating to race, sex and diet are not stated in the article. Works Cited Danilo, Christiane., Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P Lisanti and Philippe G Frank. Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signalling associated with breast cancer development. Breast Cancer Research, 15 (2013):R87 “Good cholesterol and breast cancer risk.” MNT, 13 Oct 2013. Web. 11 Dec 2013. http://www.medicalnewstoday.com/releases/267300.php Taghian, Alphonse G., Barbara L. Smith and John K. Erban. Breast cancer: a multidisciplinary approach to diagnosis and management. Demos Medical Publishing, 2009. Read More