Milani, Emanuela. PTP1B restrains mammary progenitor cells fate commitment and secretory differentiation. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10371
We found that loss of PTP1B increases the number of mammary alveolar progenitors, enhancing the pool of cells able to generate alveolar structures during pregnancy. Consistently, we observed an increase in alveolar density in glands from PTP1B-/- mice. We also found that deletion of PTP1B increased expression of milk proteins during late pregnancy. We showed that these phenotypes are mediated by precocious phosphorylation and activation of the transcription factor STAT5 and/or by increased expression of the progesterone receptor, two key regulators of mammary gland development and differentiation. These observations provide new insight into the signaling cascades that regulate mammary stem/progenitor cells differentiation and lineage commitment during mammary gland development.
In summary, we identified new functions for PTP1B in mammary gland alveologenesis and lactogenesis. The absence of PTP1B protects from, or delays HER2/Neu evoked mammary tumors in mice. Our studies raise the possibility that the change in mammary cell fate seen in glands lacking PTP1B may contribute to the observed cancer protective effect, a question that warrant further investigation.
|Committee Members:||Hynes, Nancy E. and Christofori, Gerhard|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||76 S.|
|Last Modified:||30 Jun 2016 10:52|
|Deposited On:||02 May 2013 10:24|
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