Downregulation of human FGF8 activity by antisense constructs in murine fibroblastic and human prostatic carcinoma cell systems

Oncogene
N Rudra-GangulyP Roy-Burman

Abstract

Previously, we described cloning of three alternatively spliced mRNA forms of human FGF8, a, b, and e, of which the b form is the major expressed species in both normal and tumor prostatic epithelial cells. In this report, we describe construction and overexpression of sense and antisense sequences of either the full length FGF8b coding region (215-amino acids or 215aa), 103aa N-terminal part or a smaller N-terminal region (34aa), each including the 23aa putative signal peptide domain, via a retrovirus system. While the morphologic transforming activities of the sense 215aa and 103aa constructs were similar in NIH3T3 cells, 103aa displayed reduced soft agar clonogenic activity. The 34aa construct was practically inert in these assays, although its expression could mimic the ability of 215aa or 103aa in conferring cell growth under reduced serum condition. Overexpression of any of the three constructs in antisense orientation, however, was similarly effective in reversing the morphology and anchorage-independent growth property of FGF8b-transfected NIH3T3 cells. The expression of the antisense 215aa construct significantly reduced the growth rate of the human prostatic carcinoma DU145 cells and inhibited their soft agar clonogen...Continue Reading

Citations

Jul 8, 1999·The American Journal of Pathology·J ZhengP Roy-Burman
Jun 11, 2002·Journal of Molecular Biology·Vincent BrondaniFrançois Hamy
Dec 6, 2001·Journal of the National Cancer Institute·M OzenM Ittmann
Jun 29, 2000·Biochemical and Biophysical Research Communications·V Brondani, F Hamy
May 6, 2009·Journal of Cellular Biochemistry·Maija P ValtaPirkko L Härkönen
Jun 5, 2003·British Journal of Cancer·V J GnanapragasamH Y Leung
Jul 26, 2002·Oncogene·Vincent J GnanapragasamHing Y Leung
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jianghua WangMichael Ittmann
Feb 21, 2006·Cancer Research·Chen ZhongPradip Roy-Burman
Jul 31, 2020·Physiological Reviews·Arianna GiacominiMarco Presta

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