Contact: to feature here

Thread Rating:
  • 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Genes associated with cancer pathogenesis
All biochemical processes in the human body are tightly associated with gene expression. When some elements in this complex machinery doesn’t work properly, whole cascade of events will be disturbed, resulting in some kind of pathology. Mutated genes (carrying altered information) could be inherited. List of inherited conditions is long and well studied. Besides classical inherited disorders, a lot of pathologies arise during life. Mechanisms and/or triggers for a lot of different disorders are still waiting to be discovered. Most experiments are focused on DNA material and factors (both intrinsic and extrinsic) that are disturbing various processes on the molecular level. Mostly used model organisms for genetic experiments are fruit fly (Drosophila melanogaster). They are small, have a short and well known life cycle, and could be easily cultivated in the laboratory. Although it may look that insects don’t have much in common with humans, same ancestor and highly conserved genetic sequences allow scientists to analyze wide range of human disorders using Drosophila's genetic material. Latest set of valuable information derived from fruit fly experiment could help scientists in the future fight against cancer.

There are more than 200 different cancer types. With 13% of all registered cases, this is the leading cause of death worldwide (one out of 4 deaths in USA is cancer related). Cancer could affect all body parts, and most commonly affected organs are liver, lungs, stomach, colon, rectum, cervics. Some people have high predisposition to develop certain type of carcinoma (genetically inherited). External factors could greatly accelerate cancer development. Aggressive and toxic chemicals, UV radiation, radioactive elements, injuries, viruses… are usual cancerogenesis triggers. Removal of the cancerous tissue, chemotherapy and immune system boosting are only solutions for people diagnosed with cancer, but chances of winning the battle against the cancer are still small. Metastases are main reason of death because vital organs became affected when cancer start to spread. According to current statistics, number of diagnosed cases will continue rising and it is estimated that number of cancer related deaths will reach 13.1 million by 2030 (in 2008, “just” 7.6 million deaths were cancer related).

Scientists of the Stowers Institute for Medical Research investigate molecular mechanism behind human disease. They recently discovered and published unknown facts associated with cancer pathogenesis. Fruit fly was used as a model organism. Prior genetic expression, DNA needs to be uncoiled so that the transcriptional factors and other proteins could easily approach gene of interest. Methylation and demethylation will determine if “path” to the DNA molecule will be passable. These processes are associated with certain amino acids in histones. Histone complexes are responsible for DNA condensation. Usually, demethylation of histone amino acid residues result in activation of the genetic expression, while methylation prevents genetic expression (repression). Exception from this rule is seen with methylation of the lysine and arginine amino acid residues. When lysine 4 on the histone 3 (H3K4) is methylated - expression is allowed. Same could be applied with arginine residue on histone 3 (H3) and 4 (H4). Protein named Set1/COMPASS induces methylation of the H3K4 complex. It can be mono-, di- or trimethylated, which will determine the potential of genetic enhancer to approach DNA molecule. Trimethylation is associated with transcriptionally active genes. H3K4 monomethylation is associated with genetic expression in the tissue specific manner. Yeast genome has one COMPASS methylase, human genome contains 6 different families while drosophila genome contains 3 COMPASS families. Scientists from the Stowers Institute tested importance of each family by silencing their activity and observing further genetic expression patterns. When Trr complex (short version of Trithorax-related) was silenced, H3K4 methylation was decreased in the whole genome. Silencing the remaining two families didn’t provide the same effect. Further analysis of the Trr complex showed that it is closely associated with the enhancer (activator) of the genetic expression. Without Trr complex, enhancer couldn’t be activated and genetic expression will be suppressed. Two mutated forms of the genes MLL3 and MLL4 are often present in numerous cancer types (lymphomas, colorectal cancer, medulloblastoma, breast cancer) and they structurally highly resemble Trr complex. Using mouse fibroblast lacking MLL3, scientists wanted to examine changes in the methylation. They noticed decreased H3K4 monomethylation (in the enhancer region) when MLL3 was absent. This experiment showed for the first time that MLL3 and MLL4 could be important factors in cancer pathogenesis through activation and deactivation of the specific enhancers.

Precise role and mechanism of action during suppression/activation processes still need to be discovered.
Like Post Reply
Abnormal growth of the cells results in cancer.

The cancer cells proliferate swiftly regardless of the restriction with nutrients, space and are unresponsive to the body’s stop signal. The shapes of the cancer cells are different from that of normal body cells and uncontrollably proliferate to form malignant tumors. The malignant tumors, in contrast to benign tumors, are capable of pervading to the nearby regions of the body. With the aid of bloodstream or the lymphatic system the cancer may also spread to more far-off places in the body. The study of tumors and cancers is termed as oncology and the usage of the phrase cancer implies that the tumor is malignant and can be fatal.

The revelation that certain types of genes are involved in cancer is a significant milestone in cancer research. Accordingly about 90% of the cancers are examined could be traced to some kind of genetic alteration. A part of these genetic alterations are inherited (hereditary cancers) whereas others are termed sporadic and are supposed to have arisen from gene damage resulting from various factors such as environmental exposures, hormones, aging, dietary factors etc. These acquired sporadic alterations are mostly not passed on to the children or shared amongst relatives.

The three major types of genes that can influence cell growth and are mutated in certain types of cancers are;
Oncogenes are the genes that usually direct cell growth. If the oncogenes are altered they result in cancer. Researchers describe the oncogenes as cancer switches that most individuals possess in their bodies and a sudden flip to them can activate cancer.

Mismatch-repair genes (MMR) perform numerous functions such as repair of errors in DNA synthesis. The alteration of these genes leads to increased susceptibility to various cancers.

Tumor suppressor genes are capable of recognizing abnormal growth and proliferation of the cells and halt their growth. However if the tumor suppressor genes get mutated, its functions are hindered and results in tumor development.
Like Post Reply
In humans the genes BRCA1 and BRCA2 are involved in tumor suppressor protein production. These proteins play a key role in the up keeping of the genetic material stability by repairing the damaged DNA. An alteration or mutation in either of the genes results in non functional protein product which is incapable of repairing the damaged DNA accurately. As a consequence the cells are more liable to accumulate additional genetic mutations that can direct the cell to become cancerous.

The inherited mutations in the genes BRCA1 and BRCA2 elevate the risk of breast and ovarian cancers in the females and also the genes have been linked with increased risks of developing various other cancer types. The mutations in BRCA1 and BRCA2 genes collectively account for around 20 to 25% of the breast cancers that are hereditary and around 5 to 10% of all breast cancers. Additionally the mutations in the two genes also account for about 15% of overall ovarian cancers. In comparison to the sporadic breast cancers the breast cancers associated with hereditary mutations in genes BRCA1 and BRCA2 develop at young age.

The p53 (TP53) gene encodes proteins that control the cell cycle and hence plays a key role in tumor suppression. The gene is described by the scientists as the guardian of genome as it is vital for the cells of multi-cellular creatures in cancer suppression. The name is derived from its molecular weight (53 kilodalton fraction of the cell proteins).The individual who inherits only one functioning copy of the gene p53 is prone to cancer and generally acquires various independent tumors in the adulthood. This rare condition is termed as Li-Fraumeni syndrome. Nevertheless, p53 gene mutations are found in many tumor varieties and therefore contribute to the complicated molecular events resulting in tumor formation. The gene p53 is present on chromosome number 17 of human beings.
Like Post Reply

Possibly Related Threads…
Last Post

Users browsing this thread:
1 Guest(s)

Genes associated with cancer pathogenesis00