Cargando…
PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition
This study examined the effects of parathyroid hormone-related protein (PTHrP) derived from human MDA-MB-231 breast cancer cells on the tumor growth and osteoblast inhibition. Results revealed that knocking down PTHrP expression in the breast cancer cells strikingly inhibited the formation of subcut...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753447/ https://www.ncbi.nlm.nih.gov/pubmed/23983616 http://dx.doi.org/10.7150/ijbs.7039 |
_version_ | 1782281830650609664 |
---|---|
author | Zheng, Lu Zhu, Ke Jiao, Hongli Zhao, Zhongfang Zhang, Lixiao Liu, Mo Deng, Weimin Chen, Di Yao, Zhi Xiao, Guozhi |
author_facet | Zheng, Lu Zhu, Ke Jiao, Hongli Zhao, Zhongfang Zhang, Lixiao Liu, Mo Deng, Weimin Chen, Di Yao, Zhi Xiao, Guozhi |
author_sort | Zheng, Lu |
collection | PubMed |
description | This study examined the effects of parathyroid hormone-related protein (PTHrP) derived from human MDA-MB-231 breast cancer cells on the tumor growth and osteoblast inhibition. Results revealed that knocking down PTHrP expression in the breast cancer cells strikingly inhibited the formation of subcutaneous tumors in nude mice. PTHrP knockdown dramatically decreased the levels of cyclins D1 and A1 proteins and arrested the cell cycle progression at the G1 stage. PTHrP knockdown led to the cleavage of Caspase 8 and induced apoptosis of the tumor cells. Interestingly, knocking down PTHrP increased the levels of Beclin1 and LC3-II and promoted the formation of autophagosomes. Knocking down PTHrP expression significantly reduced the abilities of the breast cancer cells to inhibit osteoblast differentiation and bone formation in vitro and in vivo. Finally, we found that PTHrP activated its own expression through an autocrine mechanism in MDA-MB-231 cells. Collectively, these studies suggest that targeting PTHrP expression in the tumor cells could be a potential therapeutic strategy for breast cancers, especially those with skeletal metastases. |
format | Online Article Text |
id | pubmed-3753447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-37534472013-08-27 PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition Zheng, Lu Zhu, Ke Jiao, Hongli Zhao, Zhongfang Zhang, Lixiao Liu, Mo Deng, Weimin Chen, Di Yao, Zhi Xiao, Guozhi Int J Biol Sci Research Paper This study examined the effects of parathyroid hormone-related protein (PTHrP) derived from human MDA-MB-231 breast cancer cells on the tumor growth and osteoblast inhibition. Results revealed that knocking down PTHrP expression in the breast cancer cells strikingly inhibited the formation of subcutaneous tumors in nude mice. PTHrP knockdown dramatically decreased the levels of cyclins D1 and A1 proteins and arrested the cell cycle progression at the G1 stage. PTHrP knockdown led to the cleavage of Caspase 8 and induced apoptosis of the tumor cells. Interestingly, knocking down PTHrP increased the levels of Beclin1 and LC3-II and promoted the formation of autophagosomes. Knocking down PTHrP expression significantly reduced the abilities of the breast cancer cells to inhibit osteoblast differentiation and bone formation in vitro and in vivo. Finally, we found that PTHrP activated its own expression through an autocrine mechanism in MDA-MB-231 cells. Collectively, these studies suggest that targeting PTHrP expression in the tumor cells could be a potential therapeutic strategy for breast cancers, especially those with skeletal metastases. Ivyspring International Publisher 2013-08-21 /pmc/articles/PMC3753447/ /pubmed/23983616 http://dx.doi.org/10.7150/ijbs.7039 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Zheng, Lu Zhu, Ke Jiao, Hongli Zhao, Zhongfang Zhang, Lixiao Liu, Mo Deng, Weimin Chen, Di Yao, Zhi Xiao, Guozhi PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title | PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title_full | PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title_fullStr | PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title_full_unstemmed | PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title_short | PTHrP Expression in Human MDA-MB-231 Breast Cancer Cells Is Critical for Tumor Growth and Survival and Osteoblast Inhibition |
title_sort | pthrp expression in human mda-mb-231 breast cancer cells is critical for tumor growth and survival and osteoblast inhibition |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753447/ https://www.ncbi.nlm.nih.gov/pubmed/23983616 http://dx.doi.org/10.7150/ijbs.7039 |
work_keys_str_mv | AT zhenglu pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT zhuke pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT jiaohongli pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT zhaozhongfang pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT zhanglixiao pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT liumo pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT dengweimin pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT chendi pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT yaozhi pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition AT xiaoguozhi pthrpexpressioninhumanmdamb231breastcancercellsiscriticalfortumorgrowthandsurvivalandosteoblastinhibition |