Group Number: 2

Britney Porter, Sandra Nguyen, Eduardo Vargas and Samender Singh Randhawa

Carcinogenesis:It is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells.

Environment:It is the physical and biological factors along with their chemical interactions that affect an organism

Environmental Carcinogen:Any of the natural or synthetic substances that can cause cancer. Such agents may be divided into chemical agents, physical agents, hormones, and viruses.

What broad category of genes are involved with carcinogenesis?

• Oncogenes• Tumor Suppressor Genes

The first oncogene was discovered in 1970 and was termed src

Oncogenes

Activated oncogenes can cause those cells that ought to die to survive and proliferate instead.

An oncogene is a gene that has the potential to cause cancer.

This graph (based on the work of E. Sinn et al, Cell 49:465,1987) shows the synergistic effect of two oncogenes. The fraction (%) of transgenic mice without tumors is shown as a function of age.

Three groups are shown:

• mice transgenic for a hyperactive myc alone (blue)

• transgenic for ras alone (green)• transgenic for both myc and ras (red)

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. The resultant protein may be termed an oncoprotein.

Proto- Oncogene

Tumor Suppressor Genes

A code for proteins that signal a cell to stop dividing and leave the cell cycle.

Unlike the oncogenes that is considered a "go" signal they are a "stop" signal.

The first tumor suppressor gene was identified by studies of retinoblastoma, a rare childhood eye tumor.

Another important tumor suppressor is the p53 tumor-suppressor protein encoded by the TP53 gene. Homozygous loss of p53 is found in 70% of colon cancers, 30–50% of breast cancers, and 50% of lung cancers. Mutated p53 is also involved in the pathophysiology of leukemias, lymphomas, sarcomas, and neurogenic tumors. Abnormalities of the p53 gene can be inherited in Li-Fraumeni syndrome (LFS), which increases the risk of developing various types of cancers. The mutations can be inherited or can arise de novo early in embryogenesis or in one of the parent's germ cells.

How would you describe the function of these genes in normal cells and in cancer cells?

Inactivation of tumor suppressor genes therefore leads to tumor development by eliminating negative regulatory proteins.

The complete sequence of events required for the development of any human cancer is not yet known.

As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation.

In its anti-cancer role, p53 works through several mechanisms:• It can activate DNA repair proteins when DNA has sustained damage.• It can induce growth arrest by holding the cell cycle at the G1/S

regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).

• It can initiate apoptosis, the programmed cell death, if DNA damage proves to be irreparable.

Tumor protein p53

P53 complexed with DNA

• Increase the amount of p53.

Additional questions for further exploration

How can oncogenes and tumor suppressor genes be used to help prevent cancer?

• Treating problems in tumor suppressor genes is more difficult. It would mean restoring normal tumor suppressor gene functions, which researchers have not yet figured out how to do effectively.

• Scientists tried to treat some cancers that have mutations in the TP53gene by inserting normal TP53genes into viruses and then trying to infect tumor cells with these viruses. This worked well in the lab, but not in human studies.

Conclusion

Many researchers are very hopeful about the future of cancer therapies using oncogenes and tumor suppressor genes, and this remains a very active area of research. There are many clinical trials under way today that could lead to better treatments for many types of cancer.

Why did we choose this question?

We choose this question because the understanding of the genes that play a role in cancer would give us a good insight of carcinogenesis. Also we wanted to get a deeper knowledge of the genetic basis of cancer.

Sourceshttp://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1963.tb13433.x/abstract http://www.ncbi.nlm.nih.gov/pubmed/14643413

http://ask.healthline.com/galecontent/carcinogen

http://cmbi.bjmu.edu.cn/news/0009/23.pdf

http://www.enotes.com/carcinogenesis-reference/carcinogenesis-172934

http://www.cancer.org/Cancer/CancerCauses/GeneticsandCancer/OncogenesandTumorSuppressorGenes/index

http://www.youtube.com/watch?v=A7bA8b3-Dhg

http://www.broadinstitute.org/education/glossary/tumor-suppressor-gene

http://www.cancer.gov/cancertopics/understandingcancer/cancer/page45