Basic fibroblast growth factor fused to a signal peptide transforms cells

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Basic fibroblast growth factor (bFGF) is a potent growth and angiogenic factor found in high concentrations in various tissues.
• Despite high bFGF levels, tissues like the brain and kidney do not exhibit active growth or angiogenesis, suggesting tightly regulated bFGF activity.
• bFGF is typically cell-associated and not released into the medium, potentially due to the absence of a secretory-signal sequence, which may prevent autostimulation.

Purpose of the Study:

• To investigate if forced secretion of bFGF can override its natural regulation.
• To determine if secreted bFGF can lead to autocrine transformation by accessing its receptor.
• To analyze the effects of forced bFGF secretion on cell morphology and tumorigenicity.

Main Methods:

• Recombinant plasmids were used to express bFGF.
• bFGF was fused with a secretory-signal sequence to enable forced secretion.
• Transformed cells were analyzed for morphological changes and tumorigenicity.

Main Results:

• bFGF alone, expressed via a recombinant plasmid, did not induce cell transformation.
• Fusion of bFGF with a secretory-signal sequence enabled its secretion and led to cell transformation.
• The resulting transformants exhibited significant morphological alterations and developed tumors, indicating tumorigenicity.

Conclusions:

• The absence of a secretory-signal sequence is crucial for regulating bFGF activity and preventing uncontrolled cell growth.
• Forced secretion of bFGF through genetic manipulation can overcome natural regulatory mechanisms.
• Secreted bFGF can induce cell transformation and tumorigenicity, highlighting the importance of bFGF regulation in preventing cancer.