The human intermediate prolactin receptor is a mammary proto-oncogene

Abstract The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was rece...

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Autores principales:	Jacqueline M. Grible, Patricija Zot, Amy L. Olex, Shannon E. Hedrick, J. Chuck Harrell, Alicia E. Woock, Michael O. Idowu, Charles V. Clevenger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4c18855c6cd74555a97c5428cf615799
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spelling	oai:doaj.org-article:4c18855c6cd74555a97c5428cf6157992021-12-02T13:24:11ZThe human intermediate prolactin receptor is a mammary proto-oncogene10.1038/s41523-021-00243-72374-4677https://doaj.org/article/4c18855c6cd74555a97c5428cf6157992021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00243-7https://doaj.org/toc/2374-4677Abstract The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. The goal of this study was to determine if a similar transforming event occurs with the hPRLr in human breast epithelial cells and to better understand the mechanism behind such transformation. hPRLrL+I co-expression in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce Stat5a tyrosine phosphorylation. Both immunohistochemical breast cancer tissue microarray data and RNA sequencing analyses using The Cancer Genome Atlas (TCGA) identified that higher hPRLrI expression associates with triple-negative breast cancer. These studies indicate the hPRLrI, when expressed alongside hPRLrL, participates in mammary transformation, and represents a novel oncogenic mechanism.Jacqueline M. GriblePatricija ZotAmy L. OlexShannon E. HedrickJ. Chuck HarrellAlicia E. WoockMichael O. IdowuCharles V. ClevengerNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jacqueline M. Grible Patricija Zot Amy L. Olex Shannon E. Hedrick J. Chuck Harrell Alicia E. Woock Michael O. Idowu Charles V. Clevenger The human intermediate prolactin receptor is a mammary proto-oncogene
description	Abstract The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. The goal of this study was to determine if a similar transforming event occurs with the hPRLr in human breast epithelial cells and to better understand the mechanism behind such transformation. hPRLrL+I co-expression in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce Stat5a tyrosine phosphorylation. Both immunohistochemical breast cancer tissue microarray data and RNA sequencing analyses using The Cancer Genome Atlas (TCGA) identified that higher hPRLrI expression associates with triple-negative breast cancer. These studies indicate the hPRLrI, when expressed alongside hPRLrL, participates in mammary transformation, and represents a novel oncogenic mechanism.
format	article
author	Jacqueline M. Grible Patricija Zot Amy L. Olex Shannon E. Hedrick J. Chuck Harrell Alicia E. Woock Michael O. Idowu Charles V. Clevenger
author_facet	Jacqueline M. Grible Patricija Zot Amy L. Olex Shannon E. Hedrick J. Chuck Harrell Alicia E. Woock Michael O. Idowu Charles V. Clevenger
author_sort	Jacqueline M. Grible
title	The human intermediate prolactin receptor is a mammary proto-oncogene
title_short	The human intermediate prolactin receptor is a mammary proto-oncogene
title_full	The human intermediate prolactin receptor is a mammary proto-oncogene
title_fullStr	The human intermediate prolactin receptor is a mammary proto-oncogene
title_full_unstemmed	The human intermediate prolactin receptor is a mammary proto-oncogene
title_sort	human intermediate prolactin receptor is a mammary proto-oncogene
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4c18855c6cd74555a97c5428cf615799
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The human intermediate prolactin receptor is a mammary proto-oncogene

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