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- Title
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis.
- Authors
Bado, Igor; Nikolos, Fotis; Rajapaksa, Gayani; Wanfu Wu; Castaneda, Jessica; Krishnamurthy, Savitri; Webb, Paul; Gustafsson, Jan-Åke; Thomas, Christoforos; Wu, Wanfu
- Abstract
<bold>Background: </bold>Upregulation of estrogen receptor beta (ERβ) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERβ and breast carcinogenesis is still missing.<bold>Methods: </bold>To study the role of ERβ in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERβ and p53 in the mammary gland epithelium. For epithelium-specific knockout of ERβ and p53, ERβ F/F and p53 F/F mice were crossed to transgenic mice that express the Cre recombinase under the control of the human keratin 14 promoter.<bold>Results: </bold>Somatic loss of ERβ significantly accelerated formation of p53-deficient mammary tumors. Loss of the receptor also resulted in the development of less differentiated carcinomas with stronger spindle cell morphology and decreased expression of luminal epithelial markers.<bold>Conclusions: </bold>Our results show that synergism between ERβ and p53 inactivation functions to determine important aspects of breast oncogenesis and cancer progression.
- Subjects
GENETICS of breast cancer; PHYSIOLOGICAL effects of estrogen; ESTROGEN receptors; ANIMAL models of cancer; CANCER invasiveness; TRANSGENIC mice; PHYSIOLOGY; GENETICS; PROTEIN metabolism; ALLELES; ANIMAL experimentation; BREAST tumors; CELL lines; EPITHELIUM; GENE expression; GENES; IMMUNOHISTOCHEMISTRY; MICE; PROGNOSIS; PROTEINS; PHENOTYPES; KAPLAN-Meier estimator; NEOPLASTIC cell transformation; GENOTYPES; METABOLISM
- Publication
Breast Cancer Research, 2017, Vol 19, p1
- ISSN
1465-5411
- Publication type
journal article
- DOI
10.1186/s13058-017-0872-z