Modulation of circadian rhythm of DNA synthesis in tumor cells by inhibiting platelet-derived growth factor signaling

Hiroo Nakagawa, Koyanagi Satoru, Yukako Kuramoto, Akiko Yoshizumi, Matsunaga Naoya, Hiroshi Shimeno, Shinji Soeda, Shigehiro Ohdo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Circadian synchronization of cell proliferation is observed not only in normal healthy tissues but also in malignant solid tumors. However, the proliferation rhythm of tumor cells is often different from that of normal cells. We reported here that the peculiar rhythm of tumor cell proliferation was modulated by inhibition of platelet-derived growth factor (PDGF) signaling. DNA synthesis in tumor cells implanted in mice showed a 24-h oscillation apparently differing from that of normal bone marrow cells. Continuous administration of AG1295 (10 μg/h, s.c.), a PDGF receptor tyrosine kinase inhibitor, substantially suppressed DNA synthesis in the implanted tumor cells but not in the healthy bone marrow cells. During the administration of this drug, the rhythm of DNA synthesis in the tumor cells was synchronized with that in bone marrow cells. The present results suggest that the circadian rhythm of DNA synthesis in tumor cells is modulated by PDGF receptor signaling, which is activated following tumor progression. Because the rhythmic patterns of clock gene expression in tumor cells did not differ significantly from those in other healthy tissues, the enhanced signal transduction of PDGF receptor may cause an alteration in the rhythmicity of tumor cell proliferation without changing in the intracellular molecular clockwork.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalJournal of Pharmacological Sciences
Volume107
Issue number4
DOIs
Publication statusPublished - Aug 29 2008

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Platelet-Derived Growth Factor
Circadian Rhythm
DNA
Neoplasms
Bone Marrow Cells
Platelet-Derived Growth Factor Receptors
Cell Proliferation
Periodicity
Signal Transduction
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Modulation of circadian rhythm of DNA synthesis in tumor cells by inhibiting platelet-derived growth factor signaling. / Nakagawa, Hiroo; Satoru, Koyanagi; Kuramoto, Yukako; Yoshizumi, Akiko; Naoya, Matsunaga; Shimeno, Hiroshi; Soeda, Shinji; Ohdo, Shigehiro.

In: Journal of Pharmacological Sciences, Vol. 107, No. 4, 29.08.2008, p. 401-407.

Research output: Contribution to journalArticle

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