Related Experiment Video
Updated: Aug 13, 2026
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Genetic strategies of tumor suppression
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA.
Abstract:
The evaluation of the cancer cell is a complex multigene process. Tumor suppressor genes that are lost or inactivated, as well as genes that are overexpressed, play key roles in tumor progression. The identification of overexpressed genes has been expedited by the presence of transforming genes in some animal retroviruses. However, tumor suppressor genes have been difficult to identify and isolate because of their loss or inactivation during tumorigenesis. By a variety of methods, summarized in this review, a few tumor suppressors have been cloned and characterized, and many more have been recognized indirectly. The general finding at this time is that the same tumor suppressors (and oncogenes) are found associated with many different tumors, that several different altered genes are found typically in the same tumors, and that other oncogenes and tumor suppressor genes seem to be characteristically altered in particular tumor types as well. Functions of tumor suppressor genes include the control of normal cell activities such as proliferation and differentiation as well as senescence, which is a special kind of differentiation in which cells lose their ability to divide. The genetic basis of senescence and identification of genes involved in overcoming senescence, leading to immortalization (i.e., indefinite growth potential), are important areas of current investigation. Our laboratory is engaged in senescence/immortalization studies as a result of our discovery that normal human mammary epithelial cells can be immortalized by DNA of the human papilloma virus. These new studies are summarized here.
Insights
Identifying cancer-driving genes is complex. Tumor suppressor genes, crucial for controlling cell growth and differentiation, are often lost or inactivated in tumors, leading to progression and immortalization.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer progression involves complex multigene alterations, including the loss/inactivation of tumor suppressor genes and overexpression of oncogenes.
- Identifying tumor suppressor genes is challenging due to their inactivation during tumorigenesis, unlike overexpressed oncogenes which are more readily identified.
Purpose of the Study:
- To review methods for identifying and characterizing tumor suppressor genes and oncogenes.
- To discuss the roles of tumor suppressor genes in cell proliferation, differentiation, and senescence.
- To summarize current research on senescence and immortalization, including laboratory findings on human papillomavirus-induced immortalization of mammary epithelial cells.
Main Methods:
- Review of various methods used for cloning and characterizing tumor suppressor genes.
- Indirect recognition of tumor suppressor gene involvement in tumorigenesis.
- Experimental studies on senescence and immortalization using human papillomavirus DNA.
Main Results:
- Common tumor suppressors and oncogenes are associated with diverse tumor types.
- Tumors often exhibit alterations in multiple genes, with some genes specific to particular cancer types.
- Normal human mammary epithelial cells can be immortalized by human papillomavirus DNA, highlighting a pathway to overcoming senescence.
Conclusions:
- Tumorigenesis is characterized by a complex interplay of altered oncogenes and tumor suppressor genes.
- Understanding senescence and the genes that overcome it is critical for comprehending cellular immortalization and cancer development.
- Human papillomavirus DNA can induce immortalization of human mammary epithelial cells, offering insights into oncogenesis.
More Related Videos
07:41A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
09:33Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:56Treatment Resistant Cancers
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...