What is the connection between skin cancer and mitosis? | Socratic
Posts about Mitosis, meiosis and cancer written by sdagar1. breaking bonds of DNA in skin cells – skin cancer; Chemicals – carcinogens eg. The relationship between mitotic rate and depth of invasion in biopsies .. Melanoma of the skin is undoubtedly the most fatal skin cancer that. Life is based on the ability of cells to reproduce, or make copies of themselves. This is done by a process called cell division = one cell divides.
The relationship between mitotic rate and depth of invasion in biopsies of malignant melanoma
Regulation of Cell Differentiation Cell differentiation is incompletely understood, but it involves the activation or inactivation of certain genes in response to the cell's interactions with its neighboring cells and with its extracellular matrix ECM.
For example, receptors on the cell will bind to specific molecular elements in the ECM, and this binding activates intracellular signal transduction pathways that turn certain genes on or off. As a result of these interactions, some genes can be expressed in a given cell, but others cannot. For example, in a muscle cell, the genes that encode the contractile proteins actin and myosin are activated, but the gene encoding for insulin synthesis is inactivated.
Terminally differentiated cells like these i. Cell-cell and cell-ECM interactions are important not only for the induction of differentiation, but also for maintenance of differentiation in some cell types. One of the hallmarks of tumor cells is that they lose their ability to sense the ECM or neighboring cells.
Regulation of Cell Division: Cell Cycle The diagram to the right summarizes events leading to cell division. Many cells in an adult are not actively in the process of replicating; this is depicted in the diagram as "cells that cease division," also known as the G0 phase or the "resting phase.
If conditions require additional cells, the cell will receive signals that promote cell division. These signals will push the cell to complete the G1 phase cell enlargement and proceed to the S-phase, during which DNA is replicated. In the G2 phase the cell prepares for division by increasing in size and replicating intracellular organelles. It then divides through mitosis the M-phase.
In a sense, the critical juncture is the transition from G1 to the S-phase. This transition is carefully regulated by multiple factors, some of which promote the transition. Genes known as proto-oncogenes can be switched on to produce proteins that protein the transition to the S-phase.
Counteracting this push to reproduce are genes known as anti-oncogenes also called tumor suppressor genes that inhibit transition to the S-phase. The video below provides a short visual summary of these events, known as the cell cycle. The two videos below summarize the signaling events that regulate the cell cycle and events occurring during the cell cycle. It is an essential process for removing cells that are stressed, damaged, or worn out. It is estimated that over 50 billions cells undergo apoptosis each day in adults.
Apoptosis is also carefully regulated through complex mechanisms. Mutations that affect these regulatory pathways have the potential to contribute to carcinogenesis by failing to eliminate abnormal neoplastic cells or by failing to eliminate cells with other mutations that are premalignant.
Defects in apoptosis can also confer resistance to chemotherapy, radiation, and immune-mediated cell destruction. Proto-oncogenes, anti-oncogenes tumor suppressor genesand apoptosis, play a central role in understanding the pathogenesis of cancer. In short, mutations and inherited abnormalities can cause these regulatory control mechanisms to become dysfunctional.
As you will see, mutations in any of these mechanisms can cause a cell to divide or survive longer than normal, and if multiple mutations affecting these regulatory mechanisms accumulate in a single cell, the cell will have lost all control with respect to cell division.
This single cell, dividing repeatedly and without regulation will create an ever expanding clone of cells which will also undergo unregulated cell division. This is the essence of cancer. Normal Cell Division The outer layer of skin epidermis is about 12 cells thick. Cells in the basal layer bottom row divide just fast enough to replenish cells that are shed. When a basal cell divides, it produces two cells.
One remains in the basal layer and retains the capacity to divide. The other migrates out of the basal layer and loses the capacity to divide. The number of dividing cells in the basal layer, therefore, stays about the same. Basal cells divide faster than needed to replenish the cells being shed, and with each division both of the two newly formed cells will often retain the capacity to divide, leading to an increased number of dividing cells.
This creates a growing mass of tissue called a "tumor" or "neoplasm. Unraveling the Origins of Cancer Source: In Percival Pott, a surgeon at St.
Bartholomew's Hospital noticed a marked increase in cases of scrotal cancer in his clinic. His patients were almost invariably chimney sweeps or "climbing boys" - poor indentured orphans who apprenticed as sweeps and were sent up chimneys to clean the flues of ash, often naked and covered in oil.
He noted that they spent hours in contact with grime and ash and they had particles of soot embedded in their skin. In the Chimney Sweepers Act was passed in Parliament, preventing master sweeps from employing children under the age of 8.
In the age was raised to 14, and in it was raised to By the use of young climbing boys was forbidden. This simple observation was important, because it suggested that an environmental exposure could play a role in causing cancer. The dials were painted by hand with small brushes, and in order to maintain a precise shape to the brush, the employees "pointed" the brushes on their tongues.
The radium, ingested in small doses over time accumulated in bone and produced bone cancer in many of the employees mostly young women. In Wynders and Graham conducted one of the earliest case-control studies suggesting a link between tobacco smoking and lung cancer. A similar conclusion was reached by Richard Doll and Bradford Hill.
They argued that a chemical in tobacco smoke caused lung cancer, but they were unable to explain the mechanism. The virologists, led by Rous, claimed that viruses caused cancer, although no such virus had been found in human studies. Epidemiologists, such as Doll and Hill, argued that exogenous chemical caused cancer, although they could not offer a mechanistic explanation for their theory or results.
The third camp, of Theodor Boveri's successors, stood at the farthest periphery. They possessed weak, circumstantial evidence that genes internal to the cell might cause cancer, but had neither the powerful human data of the epidemiologists nor the exquisite experimental insights of the chicken virologists. Great science emerges out of great contradiction, and here was a gaping rift slicing its way through the center of cancer biology.
Was human cancer caused by an infectious agent? Was it caused by an exogenous chemical? Was it caused by an internal gene? How could the three groups of scientists have examined the same elephant and returned with such radically variant opinions about its essential anatomy?
How could DES, asbestos, radiation, hepatitis virus, and a stomach bacterium all converge on the same pathological state, although in different populations and in different organs? In addition, the viral genome had inserted itself into the DNA of the cells. This was particularly remarkable, since the genome of Rous sarcoma virus is contained in single-stranded RNA. Several years later Temin and Satoshi Mizutani isolated an enzyme, which is now called reverse transcriptase, which is able to create this transformation.
Reverse transcriptase is the enzyme which HIV uses to insert itself into the genome of infected lymphocytes in humans.
In the aftermath of these findings many cancer biologists searched for evidence of retroviruses in human cancers, but none were found.
Cancer and the cell cycle | Biology (article) | Khan Academy
Temin reasoned that the Rous sarcoma virus had caused cells to become cancerous by causing genetic alterations in infected cells. However, it was possible that the genetic alterations weren't necessarily caused just by a virus. Some of the mutants were able to replicate, but were unable to cause cancer, and with these experiments, they were able to identify which gene in RSV was responsible for causing cancer.
The gene was called"Src", short for sarcoma. And because it cause a cancer, it was dubbed an "oncogene. Protein kinases are a family of proteins that act as on-off switches by attaching a phosphate group to particularly enzymes. Attaching a phosphate to one enzyme might activate it, for example. Often a kinase activated another kinase, which in turn tagged another kinase with phosphate and activated it, and this in turn might activate another in a chain reaction such that the switching on became amplified in a powerful way.
This sequence of events might then reconfigure a cell from a non-dividing state to a dividing state. Mutant Src produced an abnormally hyperactive kinase that phosphorylated all kinds of kinases within the cell and therefore turned on many of the molecular switches, including those that controlled cell division. Normal cellular Src phosphorylated the same kinases, but at a slower, more normal rate that was carefully regulated.
These observations suggested the possibility that this cancer causing viral Src was actually a normal cellular gene with had mutated. As a result, one could think of the normal precursor gene as the "proto-oncogene," which at some pointed mutated to give rise to the Src oncogene. Scientists subsequently found that a family of similar genes was present in virtually all cells. At the time techniques for imaging chromosomes were still crude, but it appeared that a small portion of one copy of chromosome 22 was missing.
They dubbed this the"Philadelphia" chromosome, since that is where they discovered it. This provided further weight to the idea that genetic alterations mutations could be involved in the occurrence of cancers. A careful examination of the cells lining the airways of smokers showed a spectrum of pathological changes ranging from swelling and thickening, to cells with premalignant changes atypia or dysplasiato clusters of cells that were malignant and represented invasive carcinoma.
This array of changes suggested to Auerbach that cancer evolved through a progression of changes from normal to cancerous over a long period of time. Late s Bruce Ames, a bacteriologist at Berkeley, was studying mutations in Salmonella and observed that mutations could enable or disable the growth of bacteria on a petri dish.
A strain of Salmonella normally unable to grow on galactose could acquire a gene mutation that enabled it to do so. By counting the number of growth enabled colonies Ames could quantify the mutation rate. Bacteria could be exposed to a certain chemical and Ames could then measure the mutation rate. He also noticed that chemicals that were mutagens also tended to be carcinogens.
Dye derivatives that were known to be potent human carcinogens caused hundreds of mutations in the bacteria, as did x-rays, benzene compounds, and nitrosoguanidine, all of which caused cancers in rats and mice. Some known carcinogens did not induce mutations in Ames's in vitro system, but his findings did provide evidence of a link between mutations and cancer.
Late s Baruch Blumberg, a biologist, found evidence that viruses caused cancer. Patients with chronic hepatitis B infection had a fold increase in risk of developing liver cancer. Blumberg concluded, "The inflammation induced by the virus in liver cells, and the associated cycle of death and repair, appeared to be responsible for the cancer Retinoblastomas follows were known to occur in two distinct patterns: The inherited form occurs early and is typically diagnosed within the first months after birth, while the sporadic form typically occurred years after birth.
Since humans have two copies of each gene, Knudson hypothesized that individuals with the familial form inherited one defective allele, which by itself was not enough to cause the cancer. With one inherited defect, however, he proposed that a mutation in the other allele could trigger the familial form of retinoblastoma. Individuals without an inherited defect would require two mutations, one in each of the two alleles in order to produce the sporadic form of the cancer. As a result, individuals with the sporadic form tended to develop retinoblastoma later in life.
Knudson called this the two-hit hypothesis of cancer. The mutated gene that was responsible was dubbed "Rb. Proto-Oncogenes and Anti-Oncogenes The retinoblastoma gene Rb is an anti-oncogene or tumor suppressor gene ; it produces a protein whose normally function is to bind to several other proteins which prevents them from activating cell division. When a cell receives normal signals to divide, it inactivates Rb by tagging it with a phosphate group. Anti-oncogenes act like recessive genes; if one of the two genes is rendered non-functional by a mutation, there is no change in cell behavior, because the other gene is still functioning.
However, if both copies of the tumor suppressor gene are knocked out, the "brakes" to cell proliferation no longer function. In the case of Rb, some persons are born with one defective copy, so they are predisposed. If the other copy mutates in a somatic cell, then they can develop a tumor. In contrast, Src is a proto-oncogene, which normally serves to activate cell division when the cell receives an appropriate signal, whereas the mutant form of the gene an oncogene causes unrestrained activation.
Michael Bishop and Harold Varmus, demonstrated that precursors of oncogenes - proto-oncogenes - existed in all normal cells. Harold Varmus, Michael Bishop, and Alfred Knudson subsequently proposed that these two abnormalities, activated proto-oncogenes and inactivated tumor suppressors, represented the critical defects in a cancer cell.
Two years later the gene on chromosome 22 was isolated and called "Bcr". The oncogene created by their fusion was called Bcr-abl. In David Baltimore's lab in Boston created a transgenic mice with the fused gene, and they developed fatal leukemia. Follow up studies then determined that Bcr-abl encoded for a protein kinase a protein that regulated other proteins by tagging them with a phosphate group. Weinberg and two other labs, working independently published their findings regarding a cancer causing gene, called "ras" from human cancer cells.
But like src again, the ras gene in normal cells was functionally different from the ras present in cancer cells. In normal cells, the ras gene encoded a tightly regulated protein that turned 'on' and 'off' like a carefully modulated switch. In cancer cells, the gene was mutated, just as Varmus and Bishop had predicted.
Mutated ras encoded a berserk, perpetually hyperactive protein permanently locked 'on'. This mutant protein produced an unquenchable signal for a cell to divide - and to keep dividing. It was the long-sought 'native' human oncogene When Philip Leder's lab introduced the oncogene c-myc into mouse breast cells, it produced only small tumors, and typically the tumors only occurred after pregnancy, suggesting that hormonal influences played a role.
Leder then created a transgenic line with two oncogenes: These grew multiple tumors, but Leder was puzzled because millions of breast cells had acquired ras and myc, but only a few dozen formed tumors.
Bert Vogelstein at Johns Hopkins Medical School collected specimens from patients who had different stages of colon cancer and tested them for the presence of four genes that coded for oncogenes or tumor suppressors.
He found that the stages of cancer progression correlated with the activation of oncogenes and the inactivation of tumor suppressor genes. Proto-oncogenes and tumor suppressor genes influence signaling pathways affecting the cell cycle. Proto-oncogenes and tumor suppressor genes encode for proteins that ultimately have effects on the cell cycle. However, it is well known that regulatory proteins often have their effect by modifying another protein, which in turn modifies yet another protein, and so forth.
This cascade of events is referred to as a signaling pathway. Ras, for instance, activates a protein called Mek. Mek in tern activates Erk, which through several intermediary steps, ultimately accelerates cell division. This cascade of steps, called the Ras-Mek-Erk pathway - is tightly regulated in normal cells, thereby ensuring tightly regulated cell division. In cancer cells, activated "Ras" chronically and permanently actives Mek, which permanently activates Erk, resulting in uncontrolled cell division - pathological mitosis.
A tumor could thus "acquire" its own blood supply by insidiously inciting a network of blood vessels around itself and then growing, in grape like clusters, around those blood vessels, a phenomenon that Folkman called tumor angiogenesis.
What is the connection between skin cancer and mitosis?
Folkman's Harvard colleague Stan Korsmeyer found other activated pathways in cancer cells, originating in mutated genes, that also blocked cell death, thus imbuing cancer cells with the capacity to resist signals.
Other pathways allowed cancer cells to acquire motility, the capacity to move from one tissue to another - initiating metastasis.
Yet other gene cascades increased cell survival in hostile environments, such that cancer cells traveling through the bloodstream could invade other organs and not be rejected or destroyed in environments not designed for survival. It is a tumor suppressor which, if mutated, increase the risk of breast cancer. In normal cells the two separate genes were carefully regulated, but when they were fused, the result was a highly overactive kinase that signaled cells to divide continually.
Humans normally make about different kinases which regulate a wide variety of cellular pathways. By tagging specific proteins with a phosphate, they basically switch a pathway on or off. Scientists at the Ciba-Geigy pharmaceutical company in Basel, Switzerland began trying to synthesize drugs that could inhibit these kinases by binding to the protein and blocking its kinase activity.
By the early s they had created dozens of them. These compounds were also found to have specificity, meaning that one drug might block the "abl" kinase but not block the "src" kinase. When the drug was added to chronic myelogenous leukemia CML cells growing in the lab, the cells died overnight. And the drug Gleevec was given to mice that had tumors from implanted CML, the tumors regressed in days, but normal cells were undamaged.
Eventually, they agreed to make a small amount of the drug and tested an initial group of 54 patients, 53 of whom responded with prompt remissions which were usually long lasting. The drug, now called Gleevec, has become the standard of care for patients with CML.
It was licensed in From The Emperor of All Maladies: The rational synthesis of a molecule to kill cancer cells - a drug designed to specifically inactivate an oncogene These cells had acquired a mutation that altered the structure of the Bcr-abl in such a way that Gleevec would no longer bind to it, although it was still able to switch on cell division.
However, in a second drug was developed that was able to bind to Gleevec-resistant Bcr-abl. The new drug is called dasatinib, and it was able to induce remission in Gleevec-resistant cases.
Since then, many more cancer-targeted drugs have been developed. These drugs differ from the original chemotherapeutic drugs in that the newer drugs target cancer cells in a highly specific way that is custom-designed to neutralize the defect in the cancer cells. This highly specific attack means that normal cells are unaffected, resulting in far fewer side effects.
The reasons for the decline differed among the major cancer types. Lung cancer was declining primarily because of prevention as a result of decreased rates of smoking. Colon cancer and cervical cancer declined primarily due to more widespread use of effective screening measures.Andrew Holland - Cell Division and Cancer
Very early colon cancer or their predecessors adenomas were more frequently being diagnosed and often treated by colonoscopy. Cervical cancers were being identified at a very early stage by more widespread use of Pap smears. Leukemia, lymphoma, and testicular cancer deaths were declining mainly because of advances in chemotherapy.
Breast cancer mortality was declining because of improvements in screening mammographysurgery, and adjuvant chemotherapy. Transition to Cancer in a Single Cell Cancer is a clonal disease, meaning that accumulated mutations in a single cell lead to unregulated proliferation, a loss of differentiation, and abnormal behavior.
With unregulated proliferation, a single cell will give rise to an ever increasing clone of similarly abnormal cells, although the progeny cells may acquire still more mutations over time. The gene abnormalities mutations may be inherited for example, defective Rb in the familial form of retinoblastoma or they may be acquired as a result of viral infection or damage to cellular DNA caused by carcinogens, e.
It is also possible for mutations to occur as random errors during cell division. There are cellular mechanisms that repair defects in DNA, but repair is not always successful. What Is a Carcinogen? In the short video clip below Dr. Defects in DNA Repair The preceding pages make it clear that cancer evolves as the result of an accumulation of mutations within a single cell. Cells have enzymes whose function is to repair defects in DNA.
The genes that encode for these enzyme repair mechanism can also be damaged by mutations. In addition, there are several inherited defects in DNA repair that increase the likelihood of transition to malignancy. For example, xeroderma pigmentosum is an inherited defect in DNA repair that causes extreme sensitivity to ultraviolet light, making them extremely vulnerable to sunburn and skin cancers.
Ultraviolet light penetrates the superficial layers of the skin, and causes damage to DNA when the radiant energy is absorbed. For more information on ultraviolet light and adverse effects of overexposure see the module on Sun Exposure. Evolution of a Cancer Morphologic Changes As mutations accumulate in a given cell, there is a progressive loss of regulation of the cell cycle, differentiation, and cell-to-cell adhesion and interaction. These changes are accompanied by progressive abnormalities in morphology appearance of the cells.
At times, changes in cellular appearance or number are normal responses to physiologic stresses.
For example, failure to exercise a muscle will result in atrophy, while repeated exercise produces hypertrophy. Increases in the number of cells can also be temporary responses to stress of some type. It is clear that further large-scale studies are needed in this regard, since our sample size was relatively small.
Mitosis, meiosis and cancer | Year 12 Human Biology
Conclusion In patients with malignant melanoma, mitotic activity along with other histopathological characteristics can indicate the depth of tumor invasion. Therefore, in incisional biopsies of melanoma, where actual depth of the tumor cannot be measured, mitotic activity might be used to roughly estimate the depth of invasion. Acknowledgments This study was conducted based on the approved MD thesis of Sara Ahovan number of thesis: Footnotes The authors report no conflicts of interest in this work.
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