Overexpression of cyclin D1 contributes to malignancy by up-regulation of fibroblast growth factor receptor 1 via the pRB/E2F pathway

Etsu Tashiro, Hiroko Maruki, Yusuke Minato, Yuichiro Doki, I. Bernard Weinstein, Masaya Imoto

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Abstract

Overexpression of cyclin D1 due to gene rearrangement, gene amplification, or simply increased transcription occurs frequently in several types of human cancers. However, overexpression of cyclin D1 in cell culture system is insufficient, by itself, to cause malignant transformation. In the present study, we found that when rodent fibroblasts that overexpress cyclin D1, but not normal fibroblasts, were treated with basic fibroblast growth factor (bFGF), there was enhanced cell cycle progression, extracellular signal-regulated kinase 2 activation, induction of anchorage-independent growth, and enhanced invasion of a Matrigel barrier. These enhanced responses to bFGF appear to be due to increased expression of fibroblast growth factor receptor 1, at both the mRNA and protein levels, in the cyclin D1-overexpressing cells. We obtained evidence that this increase in fibroblast growth factor receptor 1 expression is mediated through cyclin D1 activation of the pRB/E2F pathway. Taken together, these results suggest that in vivo cyclin D1 overexpression can enhance tumor progression, at least in part, by potentiating the stimulatory efforts of bFGF, which is often produced by stromal cells, and the growth of adjacent tumor cells.

Original languageEnglish
Pages (from-to)424-431
Number of pages8
JournalCancer Research
Volume63
Issue number2
Publication statusPublished - 2003 Jan 15

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Receptor, Fibroblast Growth Factor, Type 1
Cyclin D1
Up-Regulation
Fibroblast Growth Factor 2
Neoplasms
Fibroblasts
Gene Rearrangement
Gene Amplification
Mitogen-Activated Protein Kinase 1
Stromal Cells
Growth
Rodentia
Cell Cycle
Cell Culture Techniques
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Overexpression of cyclin D1 contributes to malignancy by up-regulation of fibroblast growth factor receptor 1 via the pRB/E2F pathway. / Tashiro, Etsu; Maruki, Hiroko; Minato, Yusuke; Doki, Yuichiro; Weinstein, I. Bernard; Imoto, Masaya.

In: Cancer Research, Vol. 63, No. 2, 15.01.2003, p. 424-431.

Research output: Contribution to journalArticle

Tashiro, Etsu ; Maruki, Hiroko ; Minato, Yusuke ; Doki, Yuichiro ; Weinstein, I. Bernard ; Imoto, Masaya. / Overexpression of cyclin D1 contributes to malignancy by up-regulation of fibroblast growth factor receptor 1 via the pRB/E2F pathway. In: Cancer Research. 2003 ; Vol. 63, No. 2. pp. 424-431.
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