This Article Full Text Full Text (PDF) Supplementary Data 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 Chang, M. Y. Articles by Prendergast, G. C. Search for Related Content PubMed PubMed Citation Articles by Chang, M. Y. Articles by Prendergast, G. C.

Bin1 Ablation in Mammary Gland Delays Tissue Remodeling and Drives Cancer Progression

¹ Lankenau Institute for Medical Research, Wynnewood, Pennsylvania; ² Department of Pathology, Duke University School of Medicine, Durham, North Carolina; and ³ Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Requests for reprints: George C. Prendergast, Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096. Phone: 610-645-8475; Fax: 610-645-8533; E-mail: prendergast{at}limr.org.

Genes that modify oncogenesis may influence dormancy versus progression in cancer, thereby affecting clinical outcomes. The Bin1 gene encodes a nucleocytosolic adapter protein that interacts with and suppresses the cell transforming activity of Myc. Bin1 is often attenuated in breast cancer but its ability to negatively modify oncogenesis or progression in this context has not been gauged directly. In this study, we investigated the effects of mammary gland–specific deletion of Bin1 on initiation and progression of breast cancer in mice. Bin1 loss delayed the outgrowth and involution of the glandular ductal network during pregnancy but had no effect on tumor susceptibility. In contrast, in mice where tumors were initiated by the ras-activating carcinogen 7,12-dimethylbenz(a)anthracene, Bin1 loss strongly accentuated the formation of poorly differentiated tumors characterized by increased proliferation, survival, and motility. This effect was specific as Bin1 loss did not accentuate progression of tumors initiated by an overexpressed mouse mammary tumor virus-c-myc transgene, which on its own produced poorly differentiated and aggressive tumors. These findings suggest that Bin1 loss cooperates with ras activation to drive progression, establishing a role for Bin1 as a negative modifier of oncogenicity and progression in breast cancer. [Cancer Res 2007;67(1):100–7]

This article has been cited by other articles:

				A. Ramalingam, J. B. Duhadaway, E. Sutanto-Ward, Y. Wang, J. Dinchuk, M. Huang, P. S. Donover, J. Boulden, L. M. McNally, A. P. Soler, et al. Bin3 Deletion Causes Cataracts and Increased Susceptibility to Lymphoma during Aging Cancer Res., March 15, 2008; 68(6): 1683 - 1690. [Abstract] [Full Text] [PDF]

				M. Y. Chang, J. Boulden, J. B. Katz, L. Wang, T. J. Meyer, A. P. Soler, A. J. Muller, and G. C. Prendergast Bin1 Ablation Increases Susceptibility to Cancer during Aging, Particularly Lung Cancer Cancer Res., August 15, 2007; 67(16): 7605 - 7612. [Abstract] [Full Text] [PDF]