TY - JOUR
T1 - Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity
AU - Ge, Kai
AU - Duhadaway, James
AU - Sakamuro, Daitoku
AU - Wechsler-Reya, Robert
AU - Reynolds, Carol
AU - Prendergast, George C.
PY - 2000
Y1 - 2000
N2 - Oncogenic activation of MYC occurs often in breast carcinoma and is associated with poor prognosis. Loss or inactivation of mechanisms that restrain MYC may therefore be involved in tumor progression. In this study, we show that the MYC-interacting adaptor protein BIN I is frequently missing in malignant breast cells and that this loss is functionally significant. BIN I was expressed in normal and benign cells and tissues but was undetectable in 6/6 estrogen receptor-positive or estrogen receptor-negative carcinoma cell lines examined. Similarly, complete or partial losses of BIN I were documented in 30/50 (60%) cases of malignant breast tissue analyzed by immuno-histochemistry or RT-PCR. Abnormalities in the organization of the BIN1 gene were apparent in only a minority of these cases, suggesting that most losses were due to epigenetic causes. Nevertheless, they were functionally significant because ectopic BIN1 induced programmed cell death in malignant cells lacking endogenous BIN1 but had no effect on the viability of benign cells. We propose that loss of BIN1 may contribute to breast cancer progression by eliminating a mechanism that restrains the ability of activated MYC to drive cell division inappropriately.
AB - Oncogenic activation of MYC occurs often in breast carcinoma and is associated with poor prognosis. Loss or inactivation of mechanisms that restrain MYC may therefore be involved in tumor progression. In this study, we show that the MYC-interacting adaptor protein BIN I is frequently missing in malignant breast cells and that this loss is functionally significant. BIN I was expressed in normal and benign cells and tissues but was undetectable in 6/6 estrogen receptor-positive or estrogen receptor-negative carcinoma cell lines examined. Similarly, complete or partial losses of BIN I were documented in 30/50 (60%) cases of malignant breast tissue analyzed by immuno-histochemistry or RT-PCR. Abnormalities in the organization of the BIN1 gene were apparent in only a minority of these cases, suggesting that most losses were due to epigenetic causes. Nevertheless, they were functionally significant because ectopic BIN1 induced programmed cell death in malignant cells lacking endogenous BIN1 but had no effect on the viability of benign cells. We propose that loss of BIN1 may contribute to breast cancer progression by eliminating a mechanism that restrains the ability of activated MYC to drive cell division inappropriately.
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U2 - 10.1002/(SICI)1097-0215(20000201)85:3<376::AID-IJC14>3.0.CO;2-1
DO - 10.1002/(SICI)1097-0215(20000201)85:3<376::AID-IJC14>3.0.CO;2-1
M3 - Article
C2 - 10652430
AN - SCOPUS:0033987640
SN - 0020-7136
VL - 85
SP - 376
EP - 383
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 3
ER -