Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity

Kai Ge, James Duhadaway, Daitoku Sakamuro, Robert Wechsler-Reya, Carol Reynolds, George C. Prendergast

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)376-383
Number of pages8
JournalInternational Journal of Cancer
Volume85
Issue number3
DOIs
StatePublished - Jan 17 2000

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Cell Death
Breast Neoplasms
Estrogen Receptors
Breast
Neoplasms
Epigenomics
Cell Division
Cell Survival
Carcinoma
Cell Line
Polymerase Chain Reaction
Genes
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity. / Ge, Kai; Duhadaway, James; Sakamuro, Daitoku; Wechsler-Reya, Robert; Reynolds, Carol; Prendergast, George C.

In: International Journal of Cancer, Vol. 85, No. 3, 17.01.2000, p. 376-383.

Research output: Contribution to journalArticle

Ge, Kai ; Duhadaway, James ; Sakamuro, Daitoku ; Wechsler-Reya, Robert ; Reynolds, Carol ; Prendergast, George C. / Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity. In: International Journal of Cancer. 2000 ; Vol. 85, No. 3. pp. 376-383.
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