Cell Growth & Differentiation, Vol 5, Issue 6 607-613, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Whey acidic protein extrinsically expressed from the mouse mammary tumor virus long terminal repeat results in hyperplasia of the coagulation gland epithelium and impaired mammary development

L Hennighausen, R McKnight, T Burdon, M Baik, RJ Wall and GH Smith
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20982.

The whey acidic protein (WAP) is a milk protein that contains a cysteine-rich motif. This characteristic WAP signature has also been found in some protease inhibitors and certain proteins involved in tissue modeling. WAP is specifically synthesized in mammary tissue from late pregnant and lactating animals, and precocious synthesis results in impaired lobuloalveolar development of the gland in some transgenic lines. To determine whether growth modulatory effects of WAP are confined to mammary tissue, we expressed the WAP gene under the control of the mouse mammary tumor virus long terminal repeat in transgenic mice. The transgene was expressed at high levels in organs with exocrine function, such as mammary and salivary glands, prostate, seminal vesicle, and the coagulation gland. In addition to impaired mammary development, we observed hyperplasia and dysplasia of the coagulation gland epithelium. These findings suggest that WAP or a member of the WAP signature family can, in certain tissue contexts, function as an epithelial growth regulator. It appears from the present study that growth regulatory effects of WAP are restricted in the mouse to the mammary and coagulation gland epithelium.

This article has been cited by other articles:

				L. Wang, N. Bhattacharyya, T. Rabi, L. Wang, and S. Banerjee Mammary carcinogenesis in transgenic mice expressing a dominant-negative mutant of DNA polymerase {beta} in their mammary glands Carcinogenesis, June 1, 2007; 28(6): 1356 - 1363. [Abstract] [Full Text] [PDF]

				C. Hu, A. Dievart, M. Lupien, E. Calvo, G. Tremblay, and P. Jolicoeur Overexpression of Activated Murine Notch1 and Notch3 in Transgenic Mice Blocks Mammary Gland Development and Induces Mammary Tumors Am. J. Pathol., March 1, 2006; 168(3): 973 - 990. [Abstract] [Full Text] [PDF]

				J. E. Maglione, E. T. McGoldrick, L. J.T. Young, R. Namba, J. P. Gregg, L. Liu, D. Moghanaki, L. G. Ellies, A. D. Borowsky, R. D. Cardiff, et al. Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes Mol. Cancer Ther., August 1, 2004; 3(8): 941 - 953. [Abstract] [Full Text] [PDF]

				Y. Li, B. Welm, K. Podsypanina, S. Huang, M. Chamorro, X. Zhang, T. Rowlands, M. Egeblad, P. Cowin, Z. Werb, et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells PNAS, December 23, 2003; 100(26): 15853 - 15858. [Abstract] [Full Text] [PDF]

				S. R. Kappeler, Z. Farah, and Z. Puhan 5'-Flanking Regions of Camel Milk Genes Are Highly Similar to Homologue Regions of Other Species and Can be Divided into Two Distinct Groups J Dairy Sci, February 1, 2003; 86(2): 498 - 508. [Abstract] [Full Text] [PDF]

				J. E. Maglione, D. Moghanaki, L. J. T. Young, C. K. Manner, L. G. Ellies, S. O. Joseph, B. Nicholson, R. D. Cardiff, and C. L. MacLeod Transgenic Polyoma Middle-T Mice Model Premalignant Mammary Disease Cancer Res., November 1, 2001; 61(22): 8298 - 8305. [Abstract] [Full Text] [PDF]

				G. Robinson, R. McKnight, G. Smith, and L Hennighausen Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation Development, January 7, 1995; 121(7): 2079 - 2090. [Abstract] [PDF]