TY - JOUR
T1 - p53: protection against tumor growth beyond effects on cell cycle and apoptosis
AU - Wang, Xuyi
AU - Simpson, Evan Rutherford
AU - Brown, Kristy A
PY - 2015
Y1 - 2015
N2 - The tumor suppressor p53 has established functions in cancer.
Specifically, it has been shown to cause cell-cycle arrest and
apoptosis in response to DNA damage. It is also one of the most
commonly mutated or silenced genes in cancer and for this reason
has been extensively studied. Recently, the role of p53 has been
shown to go beyond its effects on cell cycle and apoptosis, with
effects on metabolism emerging as a key contributor to cancer
growth in situations where p53 is lost. Beyond this, the role of p53
in the tumor microenvironment is poorly understood. The publication
by Wang and colleagues demonstrates for the first time that p53 is a key negative regulator of aromatase and, hence, estrogen production in the breast tumor microenvironment. It goes further by demonstrating that an important regulator of aromatase, the obesity-associated and tumor-derived factor prostaglandin E2, inhibits p53 in the breast adipose stroma. This review presents these findings in the context of established and emerging roles of p53 and discusses possible implications for the treatment of breast cancer.
AB - The tumor suppressor p53 has established functions in cancer.
Specifically, it has been shown to cause cell-cycle arrest and
apoptosis in response to DNA damage. It is also one of the most
commonly mutated or silenced genes in cancer and for this reason
has been extensively studied. Recently, the role of p53 has been
shown to go beyond its effects on cell cycle and apoptosis, with
effects on metabolism emerging as a key contributor to cancer
growth in situations where p53 is lost. Beyond this, the role of p53
in the tumor microenvironment is poorly understood. The publication
by Wang and colleagues demonstrates for the first time that p53 is a key negative regulator of aromatase and, hence, estrogen production in the breast tumor microenvironment. It goes further by demonstrating that an important regulator of aromatase, the obesity-associated and tumor-derived factor prostaglandin E2, inhibits p53 in the breast adipose stroma. This review presents these findings in the context of established and emerging roles of p53 and discusses possible implications for the treatment of breast cancer.
UR - http://www.ncbi.nlm.nih.gov/pubmed/26573797
U2 - 10.1158/0008-5472.CAN-15-0563
DO - 10.1158/0008-5472.CAN-15-0563
M3 - Article
VL - 75
SP - 5001
EP - 5007
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 23
ER -