Related Experiment Video

Updated: Aug 19, 2026

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

Carcinogens with diverse mutagenic activities initiate neoplastic guinea pig cells that acquire the same N-ras point

J Doniger, V Notario, J A DiPaolo

    The Journal of Biological Chemistry
    |March 15, 1987
    PubMed

    Insights

    Researchers identified the N-ras oncogene in guinea pig cancer. A specific mutation in codon 61 was consistently found, regardless of the carcinogen used, suggesting a common activation pathway for this cancer gene.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • Carcinogen exposure can lead to cellular transformation and cancer.
    • The N-ras gene is a proto-oncogene implicated in various cancers.
    • Identifying specific oncogenic mutations is crucial for understanding cancer development.

    Purpose of the Study:

    • To identify the activated oncogene in carcinogen-induced guinea pig transformation.
    • To characterize the specific genetic alterations in the identified oncogene.
    • To determine if the mutation is dependent on the type of initiating carcinogen.

    Main Methods:

    • Molecular cloning techniques were employed to isolate the activated oncogene.
    • DNA sequence analysis was performed to determine the genetic sequence and identify mutations.
    • Comparison of the guinea pig N-ras sequence with human and mouse orthologs.

    Main Results:

    • The N-ras gene was identified as the activated oncogene in guinea pig transformation.
    • A specific AT to TA transversion mutation at codon 61 was observed, leading to a glutamine to histidine substitution.
    • This identical mutation was present in all tested cell lines, irrespective of the carcinogen used (aromatic aryl hydrocarbons or alkylating agents).

    Conclusions:

    • The findings indicate that the N-ras gene is a key oncogene in guinea pig carcinogen-induced transformation.
    • The consistent mutation at codon 61 suggests a specific mutational hotspot.
    • The oncogenic activation appears to be independent of the mutagenic activity of the initiating carcinogen, pointing towards a non-mutagenic mechanism or a common downstream pathway.

    More Related Videos

    The Lambda Select cII Mutation Detection System07:08

    The Lambda Select cII Mutation Detection System

    Published on: April 26, 2018

    In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System05:45

    In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System

    Published on: January 9, 2020

    Related Concept Videos

    Abnormal Proliferation02:23

    Abnormal 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...
    Cancers Originate from Somatic Mutations in a Single Cell02:21

    Cancers Originate from Somatic Mutations in a Single Cell

    Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
    Cancer-Critical Genes I: Proto-oncogenes01:33

    Cancer-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...
    The Ras Gene02:38

    The 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...
    Small GTPases - Ras and Rho01:24

    Small GTPases - Ras and Rho

    Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
    Three regulatory proteins control their activity:
    Mutagenicity and Carcinogenicity01:25

    Mutagenicity and Carcinogenicity

    Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...