Faculty Opinions recommendation of IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development.

2002 ◽  
Author(s):  
Charles Streuli
Keyword(s):  
Mammary Gland ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Rank Signaling ◽  
Gland Development

scholarly journals IKKα Provides an Essential Link between RANK Signaling and Cyclin D1 Expression during Mammary Gland Development

Cell ◽  
2001 ◽  
Vol 107 (6) ◽  
pp. 763-775 ◽  
Author(s):  
Yixue Cao ◽  
Giuseppina Bonizzi ◽  
Tiffany N. Seagroves ◽  
Florian R. Greten ◽  
Randall Johnson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Rank Signaling ◽  
Gland Development

scholarly journals Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3577-3588 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Kyle T. Smith ◽  
Anastasia Kariagina ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Minor Role ◽  
Normal Mammary Gland ◽  
Temporal Separation ◽  
Stage Of Development ◽  
Gland Development

Abstract Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2′-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.

scholarly journals RelB/p52 NF-κB Complexes Rescue an Early Delay in Mammary Gland Development in Transgenic Mice with Targeted Superrepressor IκB-α Expression and Promote Carcinogenesis of the Mammary Gland

2005 ◽  
Vol 25 (22) ◽  
pp. 10136-10147 ◽  
Author(s):  
Elizabeth G. Demicco ◽  
Kathryn T. Kavanagh ◽  
Raphaëlle Romieu-Mourez ◽  
Xiaobo Wang ◽  
Sangmin R. Shin ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Late Pregnancy ◽  
Soft Agar ◽  
Breast Development ◽  
Mobility Shift ◽  
Sr Protein ◽  
Gland Development

ABSTRACT Classical NF-κB (p65/p50) transcription factors display dynamic induction in the mammary gland during pregnancy. To further elucidate the role of NF-κB factors in breast development, we generated a transgenic mouse expressing the IκB-α S32/36A superrepressor (SR) protein under control of the mouse mammary tumor virus (MMTV) long terminal repeat promoter. A transient delay in mammary ductal branching was observed in MMTV-SR-IκB-α mice early during pregnancy at day 5.5 (d5.5) and d7.5; however, development recovered by mid- to late pregnancy (d14.5). Recovery correlated with induction of nuclear cyclin D1 and RelB/p52 NF-κB complexes. RelB/p52 complexes induced cyclin D1 and c-myc promoter activities and failed in electrophoretic mobility shift assay to interact with IκB-α-glutathione S-transferase, indicating that their weak interaction with IκB-α can account for the observed recovery of mammary gland development. Activation of IKKα and NF-κB-inducing kinase was detected by d5.5, implicating the alternative NF-κB signaling pathway in RelB/p52 induction. Constitutively active IKKα induced p52, RelB, and cyclin D1 in untransformed mammary epithelial cells. Moreover, mouse mammary tumors induced by 7,12-dimethylbenz(a)anthracene treatment displayed increased RelB/p52 activity. Inhibition of RelB in breast cancer cells repressed cyclin D1 and c-Myc levels and growth in soft agar. These results implicate RelB/p52 complexes in mammary gland development and carcinogenesis.

scholarly journals Mice lacking cyclin D1 are small and show defects in eye and mammary gland development.

1995 ◽  
Vol 9 (19) ◽  
pp. 2364-2372 ◽  
Author(s):  
V Fantl ◽  
G Stamp ◽  
A Andrews ◽  
I Rosewell ◽  
C Dickson
Keyword(s):  
Mammary Gland ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Gland Development

scholarly journals Insight into mammary gland development and tumor prevention in a newly developed metastatic mouse model of breast cancer

2021 ◽  
Author(s):  
Briana To ◽  
Carson Broeker ◽  
Jing-Ru Jhan ◽  
Rachel Rempel ◽  
Jonathan P Rennhack ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mouse Model ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Mammary Tumors ◽  
Mammary Development ◽  
Conditional Knockout ◽  
Altered Regulation ◽  
Gland Development

The development of breast cancer has been observed due to altered regulation of mammary gland developmental processes. Thus, a better understand of the normal mammary gland development can reveal possible mechanism in how normal cells are re-programmed to become malignant cells. E2F1-4 are part of the E2F transcription factor family with varied roles in mammary development. However, little is known about the role of E2F5 in mammary gland development. A combination of scRNAseq and predictive signature tools demonstrate the presence of E2F5 in the mammary gland and showed altered activity during the various phases of mammary gland development and function. Testing the hypothesis that E2F5 regulates mammary function, we generated a mammary-specific E2F5 knockout mouse model, resulting in modest mammary gland development changes. However, after a prolonged latency the E2F5 conditional knockout mice developed highly metastatic mammary tumors with metastases in both the lung and liver. Transplantation of the tumors revealed metastases to lymph nodes that was enriched through serial transplantation. Through whole genome sequencing and RNAseq analysis we identified, and then confirmed in vivo, that Cyclin D1 was dysregulated in E2F5 conditional knockout mammary glands and tumors. Based on these findings, we propose that loss of E2F5 leads altered regulation of Cyclin D1, which facilitates the development of mammary tumors.

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