Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• The hst-2 gene was identified due to its homology with the hst-1 gene.
• Initial studies suggested hst-2 possesses transforming capabilities, but its activity was dependent on specific experimental conditions (serum-free medium).

Purpose of the Study:

• To clone and characterize the hst-2 gene and its encoded protein.
• To determine the functional properties of hst-2, including its transforming and angiogenic potential.
• To investigate the expression pattern of hst-2 in human cell lines.

Main Methods:

• Cloning of hst-2 cosmid clones from a human genomic library.
• NIH3T3 transfection assays to assess focus-forming activity.
• Cloning of hst-2 cDNA from NIH3T3 transformants.
• Nucleotide sequence analysis of the cDNA.
• Tumorigenesis assays in nude mice.
• RNA blot analysis for gene expression.

Main Results:

• The hst-2 gene encodes a 198 amino acid protein with a signal peptide, characteristic of a heparin-binding growth factor.
• hst-2 is identical to the FGF-6 gene.
• hst-2 expression in NIH3T3 cells led to effective cell transformation and the formation of well-vascularized tumors in vivo, indicating angiogenic properties.
• hst-2 gene expression was observed in human leukemia cell lines with megakaryocytic differentiation potential.

Conclusions:

• The hst-2 gene is confirmed to be FGF-6, a potent transforming and angiogenic factor.
• The findings suggest a potential role for FGF-6 in the development of certain human leukemias.
• Further research into FGF-6's role in angiogenesis and cancer is warranted.