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Cell density-dependent modulation of basic fibroblast growth factor expression by human interferon-beta.

R Singh¹, C Bucana, N Llansa

¹UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030.

International Journal of Oncology

|May 6, 2011

Summary

This summary is machine-generated.

Human renal cell carcinoma (HRCC) cell growth factor production, basic fibroblast growth factor (bFGF), is reduced by interferons (IFN-alpha and IFN-beta). This downregulation of bFGF expression is cell-density dependent, impacting angiogenesis.

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Area of Science:

Oncology
Molecular Biology
Immunology

Background:

Basic fibroblast growth factor (bFGF) production by human renal cell carcinoma (HRCC) promotes angiogenesis.
Interferon alpha (IFN-alpha) and interferon beta (IFN-beta) are known to downregulate bFGF expression and subsequently inhibit angiogenesis.

Purpose of the Study:

To investigate the mechanism by which IFN-alpha and IFN-beta downregulate bFGF expression in HRCC cells.
To determine the role of cell density in the inhibitory effects of interferons on bFGF expression.

Main Methods:

Culturing HRCC SN12PM6 cells under sparse and confluent conditions.
Quantifying bFGF-specific mRNA transcripts and cellular bFGF protein levels.
Assessing the effects of varying concentrations of IFN-alpha and IFN-beta on bFGF expression.
Measuring bFGF gene transcription rates and de novo protein synthesis.

Main Results:

HRCC cells cultured sparsely exhibited significantly higher bFGF mRNA and protein levels compared to confluent cultures.
IFN-alpha and IFN-beta inhibited bFGF mRNA and protein expression in a concentration-dependent manner, but only in sparse cultures.
IFN-beta specifically downregulated bFGF gene transcription and de novo protein synthesis in sparse cultures.

Conclusions:

The inhibitory effects of IFN-alpha and IFN-beta on bFGF expression in HRCC cells are critically dependent on cell density.
These findings highlight a potential therapeutic strategy targeting bFGF-mediated angiogenesis in HRCC by modulating interferon activity and cell density.