This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yasui, M. Articles by Monden, M. Search for Related Content PubMed PubMed Citation Articles by Yasui, M. Articles by Monden, M. Related Collections Commentary

Antisense to Cyclin D1 Inhibits Vascular Endothelial Growth Factor–Stimulated Growth of Vascular Endothelial Cells: Implication of Tumor Vascularization

Authors' Affiliations: ¹ Department of Surgery and Clinical Oncology, Graduate School of Medicine, ² Department of Pathology, School of Allied Health Science, Faculty of Medicine, and ³ Department of Clinical Evaluation of Medicine and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; and ⁴ Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York

Requests for reprints: Hirofumi Yamamoto, Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita-City, Osaka 565-0871, Japan. Phone: 81-6-6879-3251; Fax: 81-6-6879-3259; E-mail: kobunyam{at}surg2.med.osaka-u.ac.jp.

Purpose: Our aim was to determine the effects of cyclin D1 inhibition on tumor-associated neovascularization and endothelial cell growth.

Experimental Design: We have generated adenovirus system for antisense to cyclin D1 (AS CyD1) and evaluated in vitro and in vivo effects. Small interfering RNA against cyclin D1 was also used to analyze cyclin D1 inhibition-associated vascular endothelial growth factor (VEGF) regulation.

Results: The xenografts treated with adenoviral AS CyD1 showed less vessel density and displayed smaller tumor size in colon cancer cell lines HCT116 and DLD1. In vitro studies indicated that AS CyD1 decreased VEGF protein expression in DLD1 but not in HCT116. Cyclin D1 small interfering RNA caused a decrease in VEGF expression at protein and RNA levels in DLD1. A modest decrease was noted in the VEGF promoter activity, with inactivation of the STAT3 transcription factor through dephosphorylation. On the hand, the cyclin D1 inhibition plus STAT3 inhibitor markedly decreased VEGF expression in HCT116, although VEGF did not change by the STAT3 inhibitor alone. In cultures of human umbilical vein endothelial cells (HUVEC), VEGF augmented cyclin D1 expression and cell growth. AS CyD1 significantly inhibited HUVEC growth even in the presence of VEGF. AS CyD1 also significantly suppressed in vitro tube formation in VEGF-treated HUVEC and in vivo macroaneurysm formation in VEGF-treated Matrigel plug.

Conclusions: Our results suggest that cyclin D1 may play a role in the maintenance of VEGF expression and that AS CyD1 could be potentially useful for targeting both cancer cells and their microenvironment of tumor vessels.

Commentary

Antisense to Cyclin D1 Inhibits VEGF-Stimulated Growth of Vascular Endothelial Cells: Implication of Tumor Vascularization

Richard G. Pestell and Zhiping Li
Clin. Cancer Res. 2006 12: 4459-4462. [Full Text] [PDF]

This article has been cited by other articles:

				R. W. Chen, L. T. Bemis, C. M. Amato, H. Myint, H. Tran, D. K. Birks, S. G. Eckhardt, and W. A. Robinson Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma Blood, August 1, 2008; 112(3): 822 - 829. [Abstract] [Full Text] [PDF]

				R. G. Pestell and Z. Li Antisense to Cyclin D1 Inhibits VEGF-Stimulated Growth of Vascular Endothelial Cells: Implication of Tumor Vascularization Clin. Cancer Res., August 1, 2006; 12(15): 4459 - 4462. [Full Text] [PDF]