Your browser is too old
We can't provide a great video experience on old browserUpdate now
Cancer: Origin and Terminology
This Sqadia video is the demonstration of Cancer and the Immune System - I. In most organs and tissues of a mature animal, balance is usually maintained by cell renewal and cell death. Benign tumor is not capable of indefinite growth and does not invade the healthy surrounding tissue extensively. Malignant tumor is a tumor that continues to grow and becomes progressively invasive. The term cancer refers specifically to a malignant tumor. Malignant tumors exhibit metastasis. Small clusters of cancerous cells dislodge from a tumor invade the blood or lymphatic vessels. Malignant tumors or cancers are classified according to the embryonic origin of the tissue from which the tumor is derived. Most (80–90%) are carcinomas, tumors that arise from epithelial origins such as skin, gut, or the epithelial lining of internal organs and glands. The majority of cancers of the following are carcinomas Colon, Breast, Prostate, and Lung. The leukemias and lymphomas are malignant tumors. Leukemias proliferate as single cells. Lymphomas tend to grow as tumor masses. Sarcomas arise less frequent.
Malignant Transformation of Cells
Treatment of normal cultured cells with specific chemical agents, irradiation, and certain viruses can alter their morphology and growth properties. In some cases, this process leads to unregulated growth and produces cells capable of growing as tumors when they are injected into animals. Such cells are said to have undergone transformation or malignant transformation, and they often exhibit properties in vitro similar to those of cancer cells that form in vivo. Various chemical agents such as DNA-alkylating reagent and physical agents such as Ultraviolet light and ionizing radiation cause mutations have been shown to induce transformation. Induction of malignant transformation with chemical or physical carcinogens appears to involve multiple steps, at least two distinct phases. Initiation involves changes in the genome. After initiation, promoters stimulate cell division and lead to malignant transformation. Most RNA viruses replicate in the cytosol but do not induce malignant transformation. The exceptions are retroviruses, which transcribe their RNA into DNA. A reverse-transcriptase enzyme integrates the transcript into the host’s DNA. This process is similar in the cytopathic retroviruses such as HIV-1 and HIV-2. Best-studied transforming retroviruse Rous sarcoma virus carries an oncogene v-src. First evidence that oncogenes alone could induce transformation came from studies of the v-src oncogene.
Oncogenes and Cancer Induction - I
In 1971, Howard Temin proposed that a virus might acquire oncogenes from the genome of an infected cell. In the mid-1970s, J. M. Bishop and H. E. Varmus identified a DNA sequence in normal chicken cells homologous to v-src from Rous sarcoma virus. This cellular oncogene was designated c-src. Sequence comparisons of viral and cellular oncogenes reveal that they are highly conserved in evolution. The actual coding sequences of viral oncogenes corresponding proto-oncogenes exhibit a high degree of homology. A single point mutation is all that distinguishes them. It has now become apparent that most oncogenes are derived from cellular genes that encode various growth-controlling proteins. The conversion of a proto-oncogene into an oncogene appears in many cases to accompany a change In the level of expression of a normal growth-controlling protein. Homeostasis in normal tissue is maintained. If there is an imbalance either at the stage of cellular proliferation or at the stage of cell death, a cancerous state will develop.
Oncogenes and Cancer Induction – II
One category of proto-oncogenes and their oncogenic counterparts encodes proteins that induce cellular proliferation. In normal cells, the expression of growth factors and their receptors is carefully regulated. Inappropriate expression of either a growth factor or its receptor can result in uncontrolled proliferation. Other oncogenes in this category encode products that function in signal-transduction pathways or as TFs. The Src and Abl oncogenes encode tyrosine kinases. Ras oncogene encodes a GTP-binding protein. Overactivity of any of these oncogenes may result in unregulated proliferation. A second category of cancer-associated gene tumor suppressor genes, or anti-oncogenes. These encodes proteins that inhibit excessive cell proliferation. Inactivation of these results in unregulated proliferation. Tumors develop from neural precursor cells in the immature retina. The affected child has inherited a mutated Rb allele. Somatic inactivation of the remaining Rb allele leads to tumor. Over 90% of small-cell lung cancers and over 50% of breast and colon cancers are associated with mutations in p53. A third category of cancer-associated genes regulates programmed cell death. These genes encode proteins that either block or induce apoptosis. Included in this category of oncogenes is bcl-2, an anti-apoptosis gene.
Oncogenes and Cancer Induction - III
In 1972, R. J. Huebner and G. J. Todaro suggested that mutations or genetic rearrangements of proto-oncogenes are caused by carcinogens or viruses, Alter the normally regulated function of these genes converting them into potent cancer-causing oncogenes. Some malignantly transformed cells contain multiple copies of cellular oncogenes. Several groups have identified c-myc oncogenes in homogeneously staining regions (HSRs) of chromosomes from cancer cells. Some cancer cells exhibit chromosomal translocations resulting in conditions like Chronic myelogenous leukemia (CML) and Burkitt’s lymphoma. Burkitt’s lymphoma exhibit translocation between chromosome 8 to 14. Mutation in proto-oncogenes also has been associated with cellular transformation. A major mechanism by which chemical carcinogens or x-irradiation convert a proto-oncogene to oncogene. Avian leukosis virus (ALV) is a retrovirus and it does not carry any viral oncogenes yet is able to transform B cells into lymphomas. A variety of tumors have been shown to express Increased levels of growth factors or growth-factor receptors.