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Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells
The Fry gene, located on chromosome 13, is an evolutionarily conserved large protein from yeast to human. Our previous study genetically linked the Fry gene with differential susceptibility to mammary carcinogenesis, but whether Fry affects mammary gland development and function, as well as the grow...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881260/ https://www.ncbi.nlm.nih.gov/pubmed/31824855 http://dx.doi.org/10.3389/fonc.2019.01279 |
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author | Liu, Yan Chen, Xushen Gong, Zhihong Zhang, Hao Fei, Fan Tang, Xiaojiang Wang, Jie Xu, Peilin Zarbl, Helmut Ren, Xuefeng |
author_facet | Liu, Yan Chen, Xushen Gong, Zhihong Zhang, Hao Fei, Fan Tang, Xiaojiang Wang, Jie Xu, Peilin Zarbl, Helmut Ren, Xuefeng |
author_sort | Liu, Yan |
collection | PubMed |
description | The Fry gene, located on chromosome 13, is an evolutionarily conserved large protein from yeast to human. Our previous study genetically linked the Fry gene with differential susceptibility to mammary carcinogenesis, but whether Fry affects mammary gland development and function, as well as the growth of breast cancer cells, is largely unknown. To define the consequences of Fry loss in the mammary glands, we have generated mice conditionally deficient of the Fry gene in the mammary glands using the Cre-loxP recombination system. We examined multiple phenotypes with male and female homozygous Fry conditional knockout mice (Mfry) and control mice (WT), including body weight, preliminary observations (health and neurological flexes), open field locomotion, sensory abilities, auditory threshold, and glucose metabolism. The loss of Fry in the mammary glands didn't cause a significant difference in these genotypes between Mfry and WT mice. However, our data showed that Fry was required during pregnancy, while it was functionally dispensable in virgin mammary gland development. Loss of Fry led to more lateral buds, and the lobuloalveoli were smaller and showed undistended morphology in mammary glands during late pregnancy. in vitro experiment, ectopic expression of FRY could alter the morphology and significantly suppress the growth and proliferation of the breast cancer cell lines, MDA-MB-231 (ER-/PR-/HER2-, Basal-like) and BT474 (ER+/PR+/HER2+, Luminal B). The following genome-wide transcriptomic analysis of these cells suggested that FRY interacted with protein kinases relevant signaling pathways and induced massive changes in gene expression, including the activation of the Hippo/Yap pathway. Together, our data suggest that the FRY is required for mammary glands developments during pregnant periods, and affects breast cancer cell growth and proliferation. |
format | Online Article Text |
id | pubmed-6881260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68812602019-12-10 Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells Liu, Yan Chen, Xushen Gong, Zhihong Zhang, Hao Fei, Fan Tang, Xiaojiang Wang, Jie Xu, Peilin Zarbl, Helmut Ren, Xuefeng Front Oncol Oncology The Fry gene, located on chromosome 13, is an evolutionarily conserved large protein from yeast to human. Our previous study genetically linked the Fry gene with differential susceptibility to mammary carcinogenesis, but whether Fry affects mammary gland development and function, as well as the growth of breast cancer cells, is largely unknown. To define the consequences of Fry loss in the mammary glands, we have generated mice conditionally deficient of the Fry gene in the mammary glands using the Cre-loxP recombination system. We examined multiple phenotypes with male and female homozygous Fry conditional knockout mice (Mfry) and control mice (WT), including body weight, preliminary observations (health and neurological flexes), open field locomotion, sensory abilities, auditory threshold, and glucose metabolism. The loss of Fry in the mammary glands didn't cause a significant difference in these genotypes between Mfry and WT mice. However, our data showed that Fry was required during pregnancy, while it was functionally dispensable in virgin mammary gland development. Loss of Fry led to more lateral buds, and the lobuloalveoli were smaller and showed undistended morphology in mammary glands during late pregnancy. in vitro experiment, ectopic expression of FRY could alter the morphology and significantly suppress the growth and proliferation of the breast cancer cell lines, MDA-MB-231 (ER-/PR-/HER2-, Basal-like) and BT474 (ER+/PR+/HER2+, Luminal B). The following genome-wide transcriptomic analysis of these cells suggested that FRY interacted with protein kinases relevant signaling pathways and induced massive changes in gene expression, including the activation of the Hippo/Yap pathway. Together, our data suggest that the FRY is required for mammary glands developments during pregnant periods, and affects breast cancer cell growth and proliferation. Frontiers Media S.A. 2019-11-21 /pmc/articles/PMC6881260/ /pubmed/31824855 http://dx.doi.org/10.3389/fonc.2019.01279 Text en Copyright © 2019 Liu, Chen, Gong, Zhang, Fei, Tang, Wang, Xu, Zarbl and Ren. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Liu, Yan Chen, Xushen Gong, Zhihong Zhang, Hao Fei, Fan Tang, Xiaojiang Wang, Jie Xu, Peilin Zarbl, Helmut Ren, Xuefeng Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title | Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title_full | Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title_fullStr | Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title_full_unstemmed | Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title_short | Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells |
title_sort | fry is required for mammary gland development during pregnant periods and affects the morphology and growth of breast cancer cells |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881260/ https://www.ncbi.nlm.nih.gov/pubmed/31824855 http://dx.doi.org/10.3389/fonc.2019.01279 |
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