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BIN1 is a novel MYC-interacting protein with features of a tumour suppressor
D Sakamuro1, K J Elliott, R Wechsler-Reya
1Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Abstract:
BIN1 is a novel protein that interacts with the functionally critical Myc box regions at the N terminus of the MYC oncoprotein. BIN1 is structurally related to amphiphysin, a breast cancer-associated autoimmune antigen, and RVS167, a negative regulator of the yeast cell cycle, suggesting roles in malignancy and cell cycle control. Consistent with this likelihood, BIN1 inhibited malignant cell transformation by MYC. Although BIN1 is expressed in many normal cells, its levels were greatly reduced or undetectable in 14/27 carcinoma cell lines and 3/6 primary breast tumours. Deficits were functionally significant because ectopic expression of BIN1 inhibited the growth of tumour cells lacking endogenous message. We conclude that BIN1 is an MYC-interacting protein with features of a tumour suppressor.
Insights
BIN1, a novel protein interacting with MYC, acts as a tumor suppressor. Reduced BIN1 levels in carcinomas suggest its role in inhibiting malignant cell transformation and tumor growth.
Area of Science:
- Molecular biology
- Oncology
- Cell cycle regulation
Background:
- BIN1 is a novel protein interacting with the MYC oncoprotein's N-terminal Myc box regions.
- Structurally, BIN1 is related to amphiphysin and RVS167, suggesting roles in cell cycle control and malignancy.
- MYC is a known oncoprotein implicated in various cancers.
Purpose of the Study:
- To investigate the interaction between BIN1 and MYC.
- To determine the role of BIN1 in cell transformation and tumor development.
- To assess BIN1 expression levels in carcinoma cell lines and primary tumors.
Main Methods:
- Co-immunoprecipitation to study protein interactions.
- Cell transformation assays to evaluate MYC's oncogenic activity.
- Quantitative real-time PCR and Western blotting to assess BIN1 expression in cancer cells and tissues.
Main Results:
- BIN1 directly interacts with the Myc box regions of MYC.
- BIN1 inhibited MYC-induced malignant cell transformation.
- BIN1 expression was significantly reduced or absent in a majority of tested carcinoma cell lines and primary breast tumors.
- Ectopic expression of BIN1 suppressed the growth of tumor cells with low endogenous BIN1 levels.
Conclusions:
- BIN1 is an MYC-interacting protein with functional tumor suppressor activity.
- Reduced BIN1 expression is associated with malignancy and may contribute to tumor development.
- BIN1 represents a potential therapeutic target in cancers characterized by MYC dysregulation and BIN1 deficiency.