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Akt is required for Stat5 activation and mammary differentiation.

Publication ,  Journal Article
Chen, C-C; Boxer, RB; Stairs, DB; Portocarrero, CP; Horton, RH; Alvarez, JV; Birnbaum, MJ; Chodosh, LA
Published in: Breast Cancer Res
2010

INTRODUCTION: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but not Akt2, exhibit a pronounced metabolic defect during late pregnancy and lactation that results from a failure to upregulate Glut1 as well as several lipid synthetic enzymes. Despite this metabolic defect, however, both Akt1-deficient and Akt2-deficient mice exhibit normal mammary epithelial differentiation and Stat5 activation. METHODS: In light of the overlapping functions of Akt family members, we considered the possibility that Akt may play an essential role in regulating mammary epithelial development that is not evident in Akt1-deficient mice due to compensation by other Akt isoforms. To address this possibility, we interbred mice bearing targeted deletions in Akt1 and Akt2 and determined the effect on mammary differentiation during pregnancy and lactation. RESULTS: Deletion of one allele of Akt2 in Akt1-deficient mice resulted in a severe defect in Stat5 activation during late pregnancy that was accompanied by a global failure of terminal mammary epithelial cell differentiation, as manifested by the near-complete loss in production of the three principal components of milk: lactose, lipid, and milk proteins. This defect was due, in part, to a failure of pregnant Akt1(-/-);Akt2(+/-) mice to upregulate the positive regulator of Prlr-Jak-Stat5 signaling, Id2, or to downregulate the negative regulators of Prlr-Jak-Stat5 signaling, caveolin-1 and Socs2. CONCLUSIONS: Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation.

Duke Scholars

Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2010

Volume

12

Issue

5

Start / End Page

R72

Location

England

Related Subject Headings

  • Signal Transduction
  • STAT5 Transcription Factor
  • Proto-Oncogene Proteins c-akt
  • Organ Culture Techniques
  • Oncology & Carcinogenesis
  • Milk Proteins
  • Mice, Knockout
  • Mice
  • Mammary Glands, Animal
  • Lactation
 

Citation

APA
Chicago
ICMJE
MLA
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Chen, C.-C., Boxer, R. B., Stairs, D. B., Portocarrero, C. P., Horton, R. H., Alvarez, J. V., … Chodosh, L. A. (2010). Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Res, 12(5), R72. https://doi.org/10.1186/bcr2640
Chen, Chien-Chung, Robert B. Boxer, Douglas B. Stairs, Carla P. Portocarrero, Rachel H. Horton, James V. Alvarez, Morris J. Birnbaum, and Lewis A. Chodosh. “Akt is required for Stat5 activation and mammary differentiation.Breast Cancer Res 12, no. 5 (2010): R72. https://doi.org/10.1186/bcr2640.
Chen C-C, Boxer RB, Stairs DB, Portocarrero CP, Horton RH, Alvarez JV, et al. Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Res. 2010;12(5):R72.
Chen, Chien-Chung, et al. “Akt is required for Stat5 activation and mammary differentiation.Breast Cancer Res, vol. 12, no. 5, 2010, p. R72. Pubmed, doi:10.1186/bcr2640.
Chen C-C, Boxer RB, Stairs DB, Portocarrero CP, Horton RH, Alvarez JV, Birnbaum MJ, Chodosh LA. Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Res. 2010;12(5):R72.

Published In

Breast Cancer Res

DOI

EISSN

1465-542X

Publication Date

2010

Volume

12

Issue

5

Start / End Page

R72

Location

England

Related Subject Headings

  • Signal Transduction
  • STAT5 Transcription Factor
  • Proto-Oncogene Proteins c-akt
  • Organ Culture Techniques
  • Oncology & Carcinogenesis
  • Milk Proteins
  • Mice, Knockout
  • Mice
  • Mammary Glands, Animal
  • Lactation