CELL BIOLOGY ESSAY -- PATHOGENESIS OF CERVICAL CANCER
According to the Centre for Health Protection of the Department of Health (2011), cervical cancer becomes the tenth commonest cancer in Hong Kong in 2008. Cervical cancer usually arises from sexual activity and human papillomavirus (HPV) (Bellentir, 2002). In this essay, Human papillomavirus would be further discussed. For example, the signal transport pathway of HPV 16 and HPV 18, which many scientists believe that they are closely related of causing cervical cancer, as well as the HPV vaccine and chemotherapy of cervical cancer, would be discussed.
HPV as the Main Cause of Cervical Cancer
Cervical cancer usually starts from the invasion of HPV to the epidermal stratified squamous epithelium of cervix surface (N.D., 2011). HPV embeds with L1 protein. When virus enters the cell, the L1 protein layer degrades and releases the viral DNA in the nucleus of the host cell. And then the viral DNA transcribes to form mRNA, and attaches on the cellular DNA. Thus, the cellular DNA integrates. Finally it continues the translation process and produces E6 and E7 protein. HPV consists of 8 genes, oncogene E6 and E7 genes are closely related to the control of transcription process at human as well as the cell cycle. Once HPV enters the cervix cell, it triggers the HPV to have the transcription for production of viral E6 and E7 mRNA and the translation for production of E6 and E7 protein from double strand of the viral DNA. (Lin & Wu, 1990)
How E7 Protein Affects the Cell Cycle
In the normal cell cycle, after forming the G1Cdk-cyclin complex and inputting of ATP, Rb protein converts from active form to inactive one by phosphorylation (adding of phosphate group). After that, E2F transcription factor releases and triggers the gene transcription, and then mRNA translates for preparing essential materials like enzymes and protein for DNA synthesis phase (S phase). But when E7 enters the cell, it will bind with Rb protein, keep Rb protein phosphorylated, and destroy the restriction point function. The cell cannot detect whether the cell contains enough materials for carrying the following DNA synthesis phase or not. So that the E2F keeps releasing, and it is not ‘covered’ by Rb protein anymore. The cell cycle does not stop and keeps producing DNA. This uncontrollable proliferating of cell may finally turns into malignant cell (Nevins, 2001). Also, the p16 protein is also responsible for the D cyclin-Cdk4 activity. When there is few amount of p16, the D cyclin-Cdk4 complex would be more active, Rb protein would also phosphorylate and E2F would accumulate inside the cell. Therefore, p16 protein performs the similar function to E7 protein. (Nevins, 2001)
How E6 Protein Affects the Cell Cycle
For the normal cell cycle process, when DNA damages, tumor suppressor gene P53 would stop cell division and try to repair the DNA. If DNA cannot be repaired, P53 would give signal to that particular cell to death. This process calls apoptosis (?). But if E6 is presence, it would attach the ubiquitin part of P53 protein and destroy the P53. The ubiquitin is used for marking the targeted protein for the further degradation by proteasomes. Hence, if ubiquitin is blocked, no cell can be marked. And the ubiquitin cannot carry further degradation. P53 would not be able to carry out apoptosis anymore. It leads a net increase of existing cells. It results the imbalance of existing cell and dead cells. The total number of cells would increase. (Hardin, Bertoni & Kleinsmith (2011)
How the Secretion of Growth Factors Triggers Tumor Development Once the cell starts abnormally migration, all space would be occupied easily, which would disrupt the growth of the cancer cell. For further enlarging itself, the cancer cell usually secretes some growth factors like vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) to trigger the formation of blood vessel (angiogenesis),...
Please join StudyMode to read the full document