Proximal promoter sequences mediate cell-specific and elevated expression of the favorable prognosis marker TrkA in human neuroblastoma cells.

The Journal of Biological Chemistry
B B ChangD L Kilpatrick

Abstract

The nerve growth factor receptor, TrkA, has a critical role in the survival, differentiation, and function of neurons in the peripheral and central nervous systems. Recent studies have demonstrated a strong correlation between abundant expression of TrkA and a favorable prognosis of the pediatric tumor, neuroblastoma. This correlation suggests that TrkA may actively promote growth arrest and differentiation of neuroblastoma tumor cells and may be an important therapeutic target in the treatment of this disease. In the present study, we have examined the mechanistic basis for TrkA gene expression in human neuroblastoma cells. Northern blotting and nuclear run-on analyses demonstrated that transcription is a primary determinant of both cell-specific and variable expression of the TrkA gene in neuroblastoma cell lines that express it to different degrees. Cell-specific and variable transcription in neuroblastoma cells was recapitulated by transient transfection of TrkA promoter-luciferase reporter constructs, and regulatory sequences mediating these processes were localized to a 138-base pair region lying just upstream of the transcription initiation region. This neuroblastoma regulatory region formed multiple DNA-protein complexe...Continue Reading

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Citations

Nov 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alessandro LambiaseEnrico Garaci
Dec 19, 2007·Journal of Neurochemistry·Ximena Valderrama, Vikram Misra
May 16, 1998·Biochemical and Biophysical Research Communications·K NemotoT Ueyama
Jul 9, 1999·Biochimica Et Biophysica Acta·D BarettinoA Rodríguez-Peña

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