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 Kirma, N. Articles by Tekmal, R. R. Search for Related Content PubMed PubMed Citation Articles by Kirma, N. Articles by Tekmal, R. R.

Overexpression of the Colony-Stimulating Factor (CSF-1) and/or Its Receptor c-fms in Mammary Glands of Transgenic Mice Results in Hyperplasia and Tumor Formation

Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

A number of recent studies have suggested that the colony-stimulating factor (CSF-1) and its receptor c-fms may be involved in the development of mammary glands during lactation and breast cancer. To study the role of CSF-1 or its receptor in initiation of mammary tumorigenesis, we have generated two independent lines of transgenic mice that overexpress either CSF-1 or c-fms under the control of the mouse mammary tumor virus promoter. Mammary glands of the virgin CSF-1 transgenic mice show increased ductal branching, hyperplasia, dysplasia, and other preneoplastic changes, which are indicative of increased cellular proliferation. Similar changes were also evident in the mammary glands of the c-fms transgenic mice. These changes became more prominent with age and resulted in mammary tumor formation. Moreover, secondary events like dimethylbenz(a)anthracene treatment accelerated mammary tumor formation in these mice. Although the expression of estrogen receptor was not significantly changed in either of the transgenic mouse strains, progesterone receptor levels was higher in both transgenic lines as compared with the nontransgenic littermates. Expression of G1 cyclins was prominently increased in the mammary glands of both the CSF-1 and c-fms transgenic lines, suggesting increased cell cycle progression in these strains. In addition, the proliferation marker proliferating cell nuclear antigen (PCNA) and the mitogen-responsive transcription factor c-jun were also increased as compared with the nontransgenic controls. These findings, along with the histological data, support the hypothesis that CSF-1 and its receptor are involved in the etiology of breast cancer.

This article has been cited by other articles:

				E. Gonzalez-Suarez, D. Branstetter, A. Armstrong, H. Dinh, H. Blumberg, and W. C. Dougall RANK Overexpression in Transgenic Mice with Mouse Mammary Tumor Virus Promoter-Controlled RANK Increases Proliferation and Impairs Alveolar Differentiation in the Mammary Epithelia and Disrupts Lumen Formation in Cultured Epithelial Acini Mol. Cell. Biol., February 15, 2007; 27(4): 1442 - 1454. [Abstract] [Full Text] [PDF]

				C. Schalk-Hihi, H.-C. Ma, G. T. Struble, S. Bayoumy, R. Williams, E. Devine, I. P. Petrounia, T. Mezzasalma, L. Zeng, C. Schubert, et al. Protein Engineering of the Colony-stimulating Factor-1 Receptor Kinase Domain for Structural Studies J. Biol. Chem., February 9, 2007; 282(6): 4085 - 4093. [Abstract] [Full Text] [PDF]

				H. Ohno, K. Kubo, H. Murooka, Y. Kobayashi, T. Nishitoba, M. Shibuya, T. Yoneda, and T. Isoe A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol. Cancer Ther., November 1, 2006; 5(11): 2634 - 2643. [Abstract] [Full Text] [PDF]

				N. Bonafe, M. Gilmore-Hebert, N. L. Folk, M. Azodi, Y. Zhou, and S. K. Chambers Glyceraldehyde-3-Phosphate Dehydrogenase Binds to the AU-Rich 3' Untranslated Region of Colony-Stimulating Factor-1 (CSF-1) Messenger RNA in Human Ovarian Cancer Cells: Possible Role in CSF-1 Posttranscriptional Regulation and Tumor Phenotype Cancer Res., May 1, 2005; 65(9): 3762 - 3771. [Abstract] [Full Text] [PDF]