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Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma
The death rates of hepatocellular carcinoma (HCC) are extremely high due to the paucity of therapeutic options. Animal models and anecdotal clinical evidence indicate a potential role of hGH and hPRL in HCC. However, the prognostic relevance and the functional role of tumor expression of these hormo...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045410/ https://www.ncbi.nlm.nih.gov/pubmed/27102295 http://dx.doi.org/10.18632/oncotarget.8781 |
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author | Kong, Xiangjun Wu, Wenyong Yuan, Yan Pandey, Vijay Wu, Zhengsheng Lu, Xuefei Zhang, Weijie Chen, Yijun Wu, Mingming Zhang, Min Li, Gaopeng Tan, Sheng Qian, Pengxu Perry, Jo K. Lobie, Peter E. Zhu, Tao |
author_facet | Kong, Xiangjun Wu, Wenyong Yuan, Yan Pandey, Vijay Wu, Zhengsheng Lu, Xuefei Zhang, Weijie Chen, Yijun Wu, Mingming Zhang, Min Li, Gaopeng Tan, Sheng Qian, Pengxu Perry, Jo K. Lobie, Peter E. Zhu, Tao |
author_sort | Kong, Xiangjun |
collection | PubMed |
description | The death rates of hepatocellular carcinoma (HCC) are extremely high due to the paucity of therapeutic options. Animal models and anecdotal clinical evidence indicate a potential role of hGH and hPRL in HCC. However, the prognostic relevance and the functional role of tumor expression of these hormones in human HCC are not defined. Herein, we analyzed the mRNA and protein expression of hGH and hPRL in histopathological samples of non-neoplastic liver and HCC by in situ hybridization, PCR and immunohistochemistry techniques. Increased mRNA and protein expression of both hormones was observed in HCC compared with non-neoplastic liver tissues. hGH expression was significantly associated with tumor size and tumor grade. No significant association was observed between the expression of hPRL and any histopathological features. Amplification of both hGH and hPRL genes in HCC was observed when compared to non-neoplastic tissue. Expression of both hGH and hPRL was associated with worse relapse-free and overall survival in HCC patients. In vitro and in vivo functional assays performed with HCC cell lines demonstrated that autocrine expression of hGH or hPRL in HCC cells increased STAT3 activation, oncogenicity and tumor growth while functional antagonism with hGH-G120R significantly reduced these parameters. Hence, tumor expression of hGH/hPRL is associated with a worse survival outcome for patients with HCC and hGH/hPRL function as autocrine/paracrine promoters of HCC progression. |
format | Online Article Text |
id | pubmed-5045410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50454102016-10-13 Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma Kong, Xiangjun Wu, Wenyong Yuan, Yan Pandey, Vijay Wu, Zhengsheng Lu, Xuefei Zhang, Weijie Chen, Yijun Wu, Mingming Zhang, Min Li, Gaopeng Tan, Sheng Qian, Pengxu Perry, Jo K. Lobie, Peter E. Zhu, Tao Oncotarget Research Paper The death rates of hepatocellular carcinoma (HCC) are extremely high due to the paucity of therapeutic options. Animal models and anecdotal clinical evidence indicate a potential role of hGH and hPRL in HCC. However, the prognostic relevance and the functional role of tumor expression of these hormones in human HCC are not defined. Herein, we analyzed the mRNA and protein expression of hGH and hPRL in histopathological samples of non-neoplastic liver and HCC by in situ hybridization, PCR and immunohistochemistry techniques. Increased mRNA and protein expression of both hormones was observed in HCC compared with non-neoplastic liver tissues. hGH expression was significantly associated with tumor size and tumor grade. No significant association was observed between the expression of hPRL and any histopathological features. Amplification of both hGH and hPRL genes in HCC was observed when compared to non-neoplastic tissue. Expression of both hGH and hPRL was associated with worse relapse-free and overall survival in HCC patients. In vitro and in vivo functional assays performed with HCC cell lines demonstrated that autocrine expression of hGH or hPRL in HCC cells increased STAT3 activation, oncogenicity and tumor growth while functional antagonism with hGH-G120R significantly reduced these parameters. Hence, tumor expression of hGH/hPRL is associated with a worse survival outcome for patients with HCC and hGH/hPRL function as autocrine/paracrine promoters of HCC progression. Impact Journals LLC 2016-04-18 /pmc/articles/PMC5045410/ /pubmed/27102295 http://dx.doi.org/10.18632/oncotarget.8781 Text en Copyright: © 2016 Kong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Kong, Xiangjun Wu, Wenyong Yuan, Yan Pandey, Vijay Wu, Zhengsheng Lu, Xuefei Zhang, Weijie Chen, Yijun Wu, Mingming Zhang, Min Li, Gaopeng Tan, Sheng Qian, Pengxu Perry, Jo K. Lobie, Peter E. Zhu, Tao Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title | Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title_full | Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title_fullStr | Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title_full_unstemmed | Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title_short | Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
title_sort | human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045410/ https://www.ncbi.nlm.nih.gov/pubmed/27102295 http://dx.doi.org/10.18632/oncotarget.8781 |
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