Bin1: A Novel Tumor Suppressor Protein
George C. Prendergast and Daitoku Sakamuro
Bin1 is a novel gene product which offers utility as a diagnostic marker for malignant prostate cells. Bin1 (also known as amphiphysin II; amphiphysin-like protein, AMLP; and ALP) was identified through its ability to interact with and inhibit the oncogenic properties of the Myc oncoprotein and has features of a tumor suppressor protein. In preliminary clinical studies, monoclonal antibodies to Bin1 have been useful in the identification of malignant prostate cancer cells.
Bin1 structure suggests that it functions in a signal transduction pathway. This protein has features of a tumor suppressor that is widely lost in breast, prostate, and liver carcinoma. Detecting or manipulating Bin1 function in cells has potential applications for carcinoma and possibly other cancers involving Myc. Preliminary evidence suggests that Bin1 acts independently of p53. The Bin1 gene is located at a hotspot for deletion in metastatic prostate carcinoma and may be mutated in these and other tumor types, including cancers of breast, liver, and cervix.
Recent investigation of Bin1 indicates that it promotes cell differentiation (in the absence of activated Myc) and apoptosis (in its presence). Bin1 has several features of a tumor suppressor: it suppresses the oncogene activity of Myc, inhibits the growth of tumor cell lines, and has been implicated in cell differentiation and apoptosis. Thus, Bin1 is a molecule that is functionally deleted in cancer and that may have important roles in normal cell regulation.
Immunohistochemical analysis of thirty frozen cases of prostate cancer indicated that presumptive altered forms of the protein specifically accumulate to high levels in cells that are malignant, but not benign or atrophic. Prostatic intraepithelial neoplasia is also specifically stained. Thus, Bin1 may offer a needed histochemical marker for differential diagnosis and possibly prognosis of prostate cancer.
Bin1 is a new target for development of novel therapeutics and diagnostics. Bin1 sequences may be useful for research, clinical diagnostics, or clinical therapeutics against cancer or other hyperproliferative diseases. Bin1 antibodies may be useful for research, diagnostic, or therapeutic applications, including staging and possible prognosis of prostate cancer. Additionally, Bin1-derived peptides might be useful as a starting point for drug design.
Wistar is seeking sponsored research and/or a licensee to develop therapeutic and diagnostic applications of Bin1. Additionally, Wistar is seeking non-exclusive licenses for antibodies to Bin1 for use as research and/or diagnostic reagents.