Frequent activation of c-kis as a transforming gene in fibrosarcomas induced by methylcholanthrene
Science (New York, N.Y.)
|May 27, 1983
Abstract:
The DNA's from two of four methylcholanthrene-induced mouse fibrosarcomas contained transforming genes that were identical in their pattern of restriction endonuclease resistance to inactivation of biologic activity. This transforming gene was identified as the activated homolog of the Kirsten murine sarcoma virus onc gene, v-kis. The finding that a defined carcinogen reproducibly leads to activation of kis as a transforming gene should be of value in elucidating the role of oncogenes in the neoplastic process.
Insights
Researchers identified an activated oncogene, Kirsten murine sarcoma virus (v-kis), in methylcholanthrene-induced mouse fibrosarcomas. This reproducible activation by a carcinogen offers insights into oncogene roles in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Carcinogenesis
Background:
- Methylcholanthrene is a chemical carcinogen known to induce tumors.
- Oncogenes play a crucial role in the development of cancer.
- The Kirsten murine sarcoma virus (KiMSV) contains an oncogene (v-kis).
Purpose of the Study:
- To identify transforming genes in methylcholanthrene-induced mouse fibrosarcomas.
- To investigate the role of oncogenes in chemically induced carcinogenesis.
Main Methods:
- DNA extraction from methylcholanthrene-induced mouse fibrosarcomas.
- Analysis of restriction endonuclease resistance patterns of transforming genes.
- Identification of the specific oncogene involved.
Main Results:
- DNA from two of four fibrosarcomas contained transforming genes.
- These transforming genes showed identical patterns of restriction endonuclease resistance.
- The identified transforming gene was the activated homolog of the Kirsten murine sarcoma virus oncogene, v-kis.
Conclusions:
- A specific carcinogen, methylcholanthrene, reproducibly activates the v-kis oncogene.
- This activation leads to the transforming potential of the gene.
- Understanding this mechanism is valuable for elucidating the role of oncogenes in cancer.
Related Concept Videos
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...