Estrogen promotes estrogen receptor negative BRCA1-deficient tumor initiation and progression

Breast Cancer Research : BCR
Chuying WangXin-Hai Pei

Abstract

Estrogen promotes breast cancer development and progression mainly through estrogen receptor (ER). However, blockage of estrogen production or action prevents development of and suppresses progression of ER-negative breast cancers. How estrogen promotes ER-negative breast cancer development and progression is poorly understood. We previously discovered that deletion of cell cycle inhibitors p16Ink4a (p16) or p18Ink4c (p18) is required for development of Brca1-deficient basal-like mammary tumors, and that mice lacking p18 develop luminal-type mammary tumors. A genetic model system with three mouse strains, one that develops ER-positive mammary tumors (p18 single deletion) and the others that develop ER-negative tumors (p16;Brca1 and p18;Brca1 compound deletion), human BRCA1 mutant breast cancer patient-derived xenografts, and human BRCA1-deficient and BRCA1-proficient breast cancer cells were used to determine the role of estrogen in activating epithelial-mesenchymal transition (EMT), stimulating cell proliferation, and promoting ER-negative mammary tumor initiation and metastasis. Estrogen stimulated the proliferation and tumor-initiating potential of both ER-positive Brca1-proficient and ER-negative Brca1-deficient tumor cells...Continue Reading

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Citations

Jan 23, 2021·Breast Cancer Research : BCR·Feng BaiXin-Hai Pei
Feb 6, 2021·Cancers·Svetlana MiklikovaMarina Cihova
Jul 13, 2021·Fertility and Sterility·Javier García-PlanellsAntonio Diez-Juan

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Methods Mentioned

BETA
xenografts
fluorescence-activated cell sorting
flow cytometry
FACS
xenograft

Software Mentioned

Kaluza

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