scholarly journals BAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
John Maringa Githaka ◽  
Namita Tripathi ◽  
Raven Kirschenman ◽  
Namrata Patel ◽  
Vrajesh Pandya ◽  
...  

AbstractElucidation of non-canonical protein functions can identify novel tissue homeostasis pathways. Herein, we describe a role for the Bcl-2 family member BAD in postnatal mammary gland morphogenesis. In Bad3SA knock-in mice, where BAD cannot undergo phosphorylation at 3 key serine residues, pubertal gland development is delayed due to aberrant tubulogenesis of the ductal epithelium. Proteomic and RPPA analyses identify that BAD regulates focal adhesions and the mRNA translation repressor, 4E-BP1. These results suggest that BAD modulates localized translation that drives focal adhesion maturation and cell motility. Consistent with this, cells within Bad3SA organoids contain unstable protrusions with decreased compartmentalized mRNA translation and focal adhesions, and exhibit reduced cell migration and tubulogenesis. Critically, protrusion stability is rescued by 4E-BP1 depletion. Together our results confirm an unexpected role of BAD in controlling localized translation and cell migration during mammary gland development.

Reproduction ◽  
2015 ◽  
Vol 149 (6) ◽  
pp. R279-R290 ◽  
Author(s):  
Michael K G Stewart ◽  
Jamie Simek ◽  
Dale W Laird

Gap junctions formed of connexin subunits link adjacent cells by direct intercellular communication that is essential for normal tissue homeostasis in the mammary gland. The mammary gland undergoes immense remodeling and requires exquisite regulation to control the proliferative, differentiating, and cell death mechanisms regulating gland development and function. The generation of novel genetically modified mice with reduced or ablated connexin function within the mammary gland has advanced our understanding of the role of gap junctions during the complex and dynamic process of mammary gland development. These studies have revealed an important stage-specific role for Cx26 (GJA1) and Cx43 (GJB2), while Cx30 (GJB6) and Cx32 (Gjb1) can be eliminated without compromising the gland. Yet, there remain gaps in our understanding of the role of mammary gland gap junctions.


2002 ◽  
Vol 197 (1-2) ◽  
pp. 127-131 ◽  
Author(s):  
Paul A Kelly ◽  
Anne Bachelot ◽  
Cécile Kedzia ◽  
Lothar Hennighausen ◽  
Christopher J Ormandy ◽  
...  

2014 ◽  
Vol 39 (6) ◽  
pp. 699-706 ◽  
Author(s):  
Breanne M. Anderson ◽  
Mira B. MacLennan ◽  
Lyn M. Hillyer ◽  
David W.L. Ma

There is growing evidence that early developmental periods may importantly influence future breast cancer risk. Also, there is great interest in the role of dietary fat in breast cancer risk, but the role of dietary fat during pubertal mammary gland development remains poorly understood. This study investigated the effect of n-3 polyunsaturated fatty acids (PUFA) using complementary dietary and genetic approaches to examine the effect of lifelong exposure of n-3 PUFA or n-6 PUFA (control) on mammary gland development and fatty acid composition. n-3 PUFA from both diet and genetics were enriched in mammary glands as early as 3 weeks of age. Parameters related to mammary gland development, including number of terminal end buds (TEB), percent coverage of ductal tree, and infiltration of TEB, were influenced by n-3 PUFA at 3 and 4 weeks of age. Overall, findings suggest that n-3 PUFA incorporation into the mammary gland early in life plays a role in the morphological development of the mammary gland during puberty.


2011 ◽  
Vol 72 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Cristina Cellurale ◽  
Nomeda Girnius ◽  
Feng Jiang ◽  
Julie Cavanagh-Kyros ◽  
Shaolei Lu ◽  
...  

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