The PR status of the originating cell of ER/PR-negative mouse mammary tumors

Progesterone receptor (PR) is usually co-localized with estrogen receptor (ER) in normal mammary cells. It is not known whether ER/PR-negative human breast cancer arises from an ER/PR-negative cell or from an ER/PR-positive cell that later lost ER/PR. Using intraductal injection of a lentivirus to d...

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Bibliographic Details
Published in:Oncogene 2016-08, Vol.35 (31), p.4149-4154
Main Authors: Dong, J, Zhao, W, Shi, A, Toneff, M, Lydon, J, So, D, Li, Y
Format: Article
Language:English
Subjects:
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Animals
Apoptosis
Breast cancer
Care and treatment
Cell Biology
Development and progression
Epithelium
ErbB-2 protein
Estrogen receptors
Female
Gene expression
Genetic aspects
Green fluorescent protein
Green Fluorescent Proteins - analysis
Health aspects
Hormone receptors
Human Genetics
Internal Medicine
Lentivirus
Mammary Neoplasms, Experimental - chemistry
Medicine
Medicine & Public Health
Mice
Oncology
Progesterone
Receptor, ErbB-2 - analysis
Receptor, ErbB-2 - physiology
Receptors, Estrogen - analysis
Receptors, Progesterone - analysis
Retroviridae
Rodents
short-communication
Tumor cells
Tumorigenesis
Tumors
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Summary:Progesterone receptor (PR) is usually co-localized with estrogen receptor (ER) in normal mammary cells. It is not known whether ER/PR-negative human breast cancer arises from an ER/PR-negative cell or from an ER/PR-positive cell that later lost ER/PR. Using intraductal injection of a lentivirus to deliver both an oncogene (ErbB2) and a floxed green fluorescent protein (GFP) in PR Cre/+ mice, whose Cre gene is under the control of the PR promoter, we were able to trace the PR status of the infected cells as they progressed to cancer. We found that the resulting early lesions stained negative for PR in most of the cells and usually retained GFP. The resulting tumors lacked ER and PR, and 75% (15/20) of them retained the GFP signal in all tumor cells, suggesting PR was never expressed throughout the evolution of a majority of these tumors. In conclusion, our data demonstrate that ErbB2-initiated ER/PR-negative mammary tumors primarily originate from the subset of the mammary epithelium that is negative for PR and probably ER as well. These findings also provide an explanation for why antihormonal therapy fails to prevent ER-negative breast cancers.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2015.465