Debate and discussion of any biological questions not pertaining to a particular topic.
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I would just like to add, that the whole process of mitosis is a complicated process, and that mistakes can be made.
Would cells that proliferate fast, make more mistakes (thus leading to cancer) than ones that proliferate slowly?
(Or do they just get the cancer faster?)
Can a function of a cell contribute to the possibility of mutation/cancer? For example, secretory proteins?
(With soo many processes going on in the cell, that the possiblility of mistakes is higher?)
Or does cancer seem to be based on the processes of the mitotic cycle and possibly just the DNA repair system?
(And what about the availablility of resources to proceed with mitosis is adequate at the time - for example co-factors for all the DNA repair enzymes?)
(a) Would cells that proliferate fast, make more mistakes (thus leading to cancer) than ones that proliferate slowly?
(Or do they just get the cancer faster?)
Some cancers grow quite slowly - for example, renal cell (kidney) cancer is known to be slow growing. Presumably (?) this is because there is an inherently relatively low turnover rate for renal cells. Ironically, though renal cell cancer is therefore slow growing (to the consequent benefit of the afflicted patient!), the (relatively!) slower rate of tumour cell division also means that renal cell cancer is highly unsusceptible to traditional chemo (which kills actively dividing cells) and also radio-resistant (ie, isn't susceptible to radiotherapy either)
However, when you consider that embryo cells can divide very fast (about half an hour), compared with adult cells ("a fairly rapidly dividing mammalian cell would have a cycle time of 12-14 hours") one might assume that therefore embryos would be far more susceptible to cancer than adults? Yet I don't think this is so???
Nevertheless, some cancers do seem to be far more aggressive than others, but whether this is because their 'natural' cell cycling time is faster (and therefore, as you surmise, the mutated/cancer cells divide faster as well), or whether this is because the mutations in the cancer cells are so severe and prevalent that the cancer is a very high grade one, I don't know.
(b) Or does cancer seem to be based on the processes of the mitotic cycle and possibly just the DNA repair system?
Yes, would seem to be the answer. It's the failure of the checkpoint processes to prevent damaged DNA from replicating, processes which usually operate just before the cell goes from G1 (growth) into S (DNA replicatino/synthesis), and then again from G2 into M (mitosis), that allows DNA-damaged cells to divide (and potentially form a malignant tumour).
RB and p53 gene products are critical proteins in regulating and enforcing these checkpoints (eg "RB acts as an 'off switch' for entry into S phase by binding the transcription factor E2F required for expression of the S-phase genes"). p53 also acts at the G2/M transition stage.
Both RB and p53 genes are (therefore) tumour suppressors. If their gene products are inactivated (by phosphorylation, eg, RB protein phosphoryalated by CDK - cyclin dependent kinase), then the cell has no means to stop damaged DNA from replicating itself, and the cell containing it to divide. (In normal mitosis, cells with damaged DNA is either sent for DNA-repair, or killed off, but not allowed to divide and replicate.)
"Mutations inactivating RB or the RB pathway are ubiquitous in cancer cells...virtually all human tumours deregulate either the pRB or p53 pathways and likely in most cases both"
(Quotes from "The Molecular Biology of Cancer" - Pelangaris and Khan. Highly recommended text - very straightforward and easy to understand, considering it's dealing with fiendishly complicated biochemical pathways!!!)
Hope this helps!
I'd like to briefly address some points about cancer. These are not absolute truths (as there are hundreds of subtypes of cancer with different characteristics), so regard these more like general rules:
a) The quicker the cell division rate a cancer has the easier it is to cure if spotted in time - the faster a cell divides the more effective are chemoterapeutics and irradiation. This is valid for healthy tissues as well: radiation, for example, is highly dangerous for intestinal epithelia, but muscles and the brain can withstand much greater doses.
b) The older the tissue / cell is the more likely it is to develop cancer. Embryos do not suffer from cancer, because there has been not enough time for all the mutations to accumulate that are required for cancer development. The older an individual is the more likely it is that their cells have several mutations, which make them more likely to turn into cancer cells. Persons that have some "cancer genes" inherited from their parents, i.e. inheritable mutations that are linked to cancer typically develop cancer at much younger age, because they already have one of the required mutations for cancer.
c) The faster the cells divide in a tissue the more likely they are to become cancerous. Blood cells and epithelia have a very high turnover rates and subsequently also big number of cancers. Brain or muscle cancers, for example, are rare as these cells hardly divide at all - thus accumulating fewer mutations and even if they mutate, they usually do not divide. Even brain tumours are usually derived from other cell types than neurons.
d) Tissues that are exposed to toxins (e.g. tobacco smoke + lungs or alcohol + liver), chemicals or physical hazards (e.g. sunlight + skin) are more susceptible to cancer.
e) Immune suppression makes people prone for cancer. Old age may slightly weaken the immune system, but a typical example is AIDS. Cells undergo malignant changes in the body quite often, but a healthy immune system can often spot these and destroy the cells that have gained detrimental mutations. With conditions such as AIDS there are no CD4+ T cells to help the immune system, and malignancies occur more easily. Kaposi's sarcoma is a typical example of a malignancy where a virus has turned the cell into a cancer cell, and the immune system cannot eradicate it anymore.
f) Some viral infections make cells prone for cancer. Especially viruses that insert their genetic material into the host genome may cause cancer, although healthy immune system typically manages to kill the virus-infected cells. HBV-infection usually stays latent in some B cells in the body (as well as some other cell types), and if there is a prolonged immune suppression, these cells may cause acute leukaemia when they start to divide because the weakened immune system cannot keep the virally immortalized cells at bay.
Hope this helps as well!
5 posts • Page 1 of 1
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