Archive for the ‘cell cycle’ Category

Cells Divide

Posted: February 27, 2011 in cell cycle, disorders, genetics

Here is a helpful study tool for the cell cycle: NOVA’s comparison of mitosis and meiosis

This is a great paper about cell cycle control – I also recommend you peruse PLoS regularly to find new, relevant information to help answer all your questions 🙂

Aberrant cell division is what we call cancer – cells that deny their place as a cooperative, sacrificial part of our body and instead replicate at our expense. All cancers are unique; additionally, it likely takes more than three independent events to give rise to a cancer cell. Thus, a “cure” for cancer is an ungrounded fantasy. However, there are two main characteristics that fundamentally link all cancers and their lack of cell cycle regulation: Lack of density-dependent inhibition and loss of anchorage control.

The initial discoveries of genetic alterations leading to cancer formation were gain-of-function mutations – these changes, creating mutant oncogenes, occur in normal cellular protooncogenes. The products of protooncogenes function in signal transduction pathways that promote cell proliferation. Studies suggest multiple, distinct pathways of genetic alteration lead to cancer, but that not all pathways have the same role in each cell type.

The significance of loss-of-function mutations has lately gained appreciation as well. The consequences of mutations in these tumor suppressor genes are not fully understood, though evidence suggests several encode proteins that prevent cell cycle progression through the division process. When functioning properly, tumor suppressor genes negate entry into or completion of the S, G2, or M phases. If protooncogenes are the accelerator when cells purposefully undergo division, tumor suppressor genes may be the brakes that halt them when growth is unnecessary.

So what does it means to “inherit” a predisposition to cancer? If cancer runs in your family, why might you be more likely to “get” it than others? Remember, now, that while you have a total of 46 chromosomes, your genome is in reality composed of two sets of 23 chromosomes. That is, you inherit one version of each chromosome from mom, and one from dad. These homologous chromosomes each hold the same genes in the same locations (termed loci) – but you may have gotten different versions – called gene variants or alleles – of these genes from each parent (and this still is only two of what may be hundreds of different versions available in our population’s collective gene pool). At any given loci (since we have ~20,000-25,000 genes, there are that number of loci in our genomes), you may have two different alleles; being a hybrid for any gene is termed heterozygous. Thus you potentially could inherit a faulty copy of the gene from one parent and a healthy copy from the other. Alternatively, you could have two healthy copies or two faulty copies – termed homozygous. How this affects you is largely speculation, though we can, in hindsight, observe trends and create percent likelihood values.

Tumor suppressor genes were initially recognized to have a major role in inherited cancer susceptibility. Because inactivation of both copies of a tumor suppressor gene is required for loss of function, individuals heterozygous  for mutations at the locus are phenotypically normal. Thus, unlike gain-of-function mutations, loss-of-function tumor suppressor mutations can be carried in the gene pool with no direct deleterious consequence. However, individuals heterozygous for tumor suppressor mutations are more likely to develop cancer, because only one mutational event is required to prevent synthesis of any functional gene product (Collins et al. 1997).

“Somewhere, in what had been up until then a near perfectly harmonious community of some one hundred trillion cells, a normal cell becomes a cancer cell. There is no sharp jab of pain to mark the event. There is no “festering” at the site of the transformation. There is no rallying of the immune system. The body accepts the cell as if it were one of its own (which it is), still under the control of the collective whole (which it is not).

For a long time, maybe twenty or thirty years, the cancer cell divides again and again. Even when its descendants number in the billions, the body exhibits no readily apparent sign or symptom of what has by then become a semi-independent mass with its own blood supply. By this time some tiny “gangs” of cancer cells have broken away from the original mass and have started thriving colonies in the brain and in the lungs, places to which the “colonists” were carried by the blood stream.

About the time the original mass reaches the ten-billion cell size, the body notices a lump.” From Dimensions of Cancer, by Charles E. Kupchella.