title: The PR status of the originating cell of ER/PR-negative mouse mammary tumors.
abstract: 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.
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.|Department of Breast Surgery, First Hospital of Jilin University, Changchun, China.
authors.forename: A
authors.initials: A
authors.lastname: Shi
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Toneff
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lydon
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: So
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Y
authors.identifier: 0000-0002-9976-518X
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D049452:Green Fluorescent Proteins / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry*; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000502:physiology; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
chemical_list: D049452:Green Fluorescent Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human