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Acquisition of transforming properties by FYN, a normal SRC-related human gene
T Kawakami1, Y Kawakami, S A Aaronson
1Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Abstract:
The SRC gene is the prototype for a family of closely related genes whose products have protein-tyrosine kinase activity. We recently described another member of this family, designated FYN, whose cDNA was isolated from normal human fibroblasts. To examine the possible role of FYN as an oncogene, we investigated the effects of FYN overexpression on NIH 3T3 cells. Our findings demonstrate that normal FYN overexpression induces morphologic transformation and anchorage-independent growth. In addition, at relatively low frequency, FYN acquired properties of a dominant-acting oncogene capable of inducing the fully tumorigenic phenotype. Genetic changes associated with the conversion of normal FYN cDNA into a transforming gene with high focus-forming activity were localized to the carboxyl-terminal region of its translational product.
Insights
The FYN gene, a member of the SRC family, can act as an oncogene. Overexpression of FYN in NIH 3T3 cells induced cell transformation and tumor formation, with key genetic changes in its carboxyl-terminal region.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- The SRC gene family encodes protein-tyrosine kinases.
- FYN is a recently identified member of the SRC gene family, isolated from human fibroblasts.
- The oncogenic potential of FYN has not been fully elucidated.
Purpose of the Study:
- To investigate the role of FYN as a potential oncogene.
- To determine the effects of FYN overexpression on NIH 3T3 cells.
- To identify genetic alterations associated with FYN's oncogenic activity.
Main Methods:
- Overexpression of normal FYN cDNA in NIH 3T3 cells.
- Assessing morphologic transformation and anchorage-independent growth.
- Analyzing genetic changes in FYN associated with oncogenic conversion.
Main Results:
- Normal FYN overexpression induced morphologic transformation and anchorage-independent growth in NIH 3T3 cells.
- FYN acquired dominant-acting oncogene properties, leading to a fully tumorigenic phenotype at low frequency.
- Genetic alterations driving high focus-forming activity were mapped to the carboxyl-terminal region of FYN.
Conclusions:
- FYN can function as an oncogene, inducing cellular transformation and tumorigenesis.
- Specific genetic changes, particularly in the carboxyl-terminal region, enhance FYN's oncogenic potential.
- FYN represents a significant target for understanding cancer development and potential therapeutic strategies.