Bcl-2 family proteins in breast development and cancer: could Mcl-1 targeting overcome therapeutic resistance?

Apoptosis, cell death executed by caspases, is essential to normal breast development and homeostasis. Pro-apoptotic and anti-apoptotic signals are tightly regulated in normal breast epithelial cells. Dysregulation of this balance is required for breast tumorigenesis and increases acquired resistanc...

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Published in:Oncotarget 2015-02, Vol.6 (6), p.3519-3530
Main Authors: Williams, Michelle M, Cook, Rebecca S
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Breast - cytology
Breast - growth & development
Breast - metabolism
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Female
Humans
Mammary Glands, Animal - cytology
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - metabolism
Myeloid Cell Leukemia Sequence 1 Protein - genetics
Myeloid Cell Leukemia Sequence 1 Protein - metabolism
Myeloid Cell Leukemia Sequence 1 Protein - physiology
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-bcl-2 - physiology
Review
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description Apoptosis, cell death executed by caspases, is essential to normal breast development and homeostasis. Pro-apoptotic and anti-apoptotic signals are tightly regulated in normal breast epithelial cells. Dysregulation of this balance is required for breast tumorigenesis and increases acquired resistance to treatments, including molecularly targeted therapies, radiation and chemotherapies. The pro-apoptotic or anti-apoptotic Bcl-2 family members interact with each other to maintain mitochondrial integrity and regulate cellular commitment to apoptosis. Among the anti-apoptotic Bcl-2 family members, Mcl-1 is uniquely regulated by numerous oncogenic signaling pathways. This review will focus on the role of Bcl-2 family proteins in normal breast development, breast tumorigenesis and acquired resistance to breast cancer treatment strategies, while highlighting Mcl-1 as a promising target to improve breast cancer tumor cell killing.
doi_str_mv 10.18632/oncotarget.2792
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subjects Animals
Apoptosis - physiology
Breast - cytology
Breast - growth & development
Breast - metabolism
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Female
Humans
Mammary Glands, Animal - cytology
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - metabolism
Myeloid Cell Leukemia Sequence 1 Protein - genetics
Myeloid Cell Leukemia Sequence 1 Protein - metabolism
Myeloid Cell Leukemia Sequence 1 Protein - physiology
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-bcl-2 - physiology
Review
title Bcl-2 family proteins in breast development and cancer: could Mcl-1 targeting overcome therapeutic resistance?
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