Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression.


Journal article


K. Toyo-oka, T. J. Bowen, S. Hirotsune, Zirong Li, Sonia Jain, S. Ota, L. Escoubet-Lozach, Ivan Garcia-Bassets, J. Lozach, M. Rosenfeld, C. Glass, R. Eisenman, Bing Ren, P. Hurlin, A. Wynshaw-Boris
Cancer research, vol. 66(11), 2006, pp. 5565-5573

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APA   Click to copy
Toyo-oka, K., Bowen, T. J., Hirotsune, S., Li, Z., Jain, S., Ota, S., … Wynshaw-Boris, A. (2006). Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression. Cancer Research, 66(11), 5565–5573.


Chicago/Turabian   Click to copy
Toyo-oka, K., T. J. Bowen, S. Hirotsune, Zirong Li, Sonia Jain, S. Ota, L. Escoubet-Lozach, et al. “Mnt-Deficient Mammary Glands Exhibit Impaired Involution and Tumors with Characteristics of Myc Overexpression.” Cancer research 66, no. 11 (2006): 5565–5573.


MLA   Click to copy
Toyo-oka, K., et al. “Mnt-Deficient Mammary Glands Exhibit Impaired Involution and Tumors with Characteristics of Myc Overexpression.” Cancer Research, vol. 66, no. 11, 2006, pp. 5565–73.


BibTeX   Click to copy

@article{k2006a,
  title = {Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression.},
  year = {2006},
  issue = {11},
  journal = {Cancer research},
  pages = {5565-5573},
  volume = {66},
  author = {Toyo-oka, K. and Bowen, T. J. and Hirotsune, S. and Li, Zirong and Jain, Sonia and Ota, S. and Escoubet-Lozach, L. and Garcia-Bassets, Ivan and Lozach, J. and Rosenfeld, M. and Glass, C. and Eisenman, R. and Ren, Bing and Hurlin, P. and Wynshaw-Boris, A.}
}

Abstract

The proto-oncogene c-Myc plays a central role in cell growth and the development of human tumors. c-Myc interacts with Max and Myc-Max complexes bind to E-box and related sequences to activate transcription. Max also interacts with Mnt but Mnt-Max complexes repress transcription when bound to these sequences. MNT maps to human chromosome 17p13.3, a region frequently deleted in various human tumors, including mammary gland tumors. Consistent with the possibility that Mnt functions as a Myc antagonist, Mnt-deficient fibroblasts exhibit many of the hallmark characteristics of cells that overexpress Myc, and conditional (Cre/Lox) inactivation of Mnt in mammary gland epithelium leads to adenocarcinomas. Here, we further characterize mammary gland tissue following conditional deletion of Mnt in the mammary gland. We show that loss of Mnt severely disrupts mammary gland involution and leads to hyperplastic ducts associated with reduced numbers of apoptotic cells. These findings suggest that loss of Mnt in mammary tissue has similarities to Myc overexpression. We tested this directly by using promoter array analysis and mRNA expression analysis by oligonucleotide arrays. We found that Mnt and c-Myc bound to similar promoters in tumors from MMTV-c-Myc transgenic mice, and mRNA expression patterns were similar between mammary tumors from MMTV-Cre/Mnt(KO/CKO) and MMTV-c-Myc transgenic mice. These results reveal an important role for Mnt in pregnancy-associated mammary gland development and suggest that mammary gland tumorigenesis in the absence of Mnt is analogous to that caused by Myc deregulation.





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