Characterization of tumor differentiation factor (TDF) and its receptor (TDF-R)
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Cellular and Molecular Life Sciences
REVIEW
Characterization of tumor differentiation factor (TDF) and its receptor (TDF-R) Izabela Sokolowska • Alisa G. Woods Mary Ann Gawinowicz • Urmi Roy • Costel C. Darie
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Received: 8 August 2012 / Revised: 27 September 2012 / Accepted: 1 October 2012 / Published online: 18 October 2012 Springer Basel 2012
Abstract Tumor differentiation factor (TDF) is an underinvestigated protein produced by the pituitary with no definitive function. TDF is secreted into the bloodstream and targets the breast and prostate, suggesting that it has an endocrine function. Initially, TDF was indirectly discovered based on the differentiation effect of alkaline pituitary extracts of the mammosomatotropic tumor MtTWlO on MTW9/PI rat mammary tumor cells. Years later, the cDNA clone responsible for this differentiation activity was isolated from a human pituitary cDNA library using expression cloning. The cDNA encoded a 108-amino-acid polypeptide that had differentiation activity on MCF7 breast cancer cells and on DU145 prostate cancer cells in vitro and in vivo. Recently, our group focused on identification of the TDF receptor (TDF-R). As potential TDF-R candidates, we identified the members of the Heat Shock 70-kDa family of proteins (HSP70) in both MCF7 and BT-549 human breast cancer cells (HBCC) and PC3, DU145, and LNCaP human prostate cancer cells (HPCC), but not in HeLa cells, NG108 neuroblastoma, or HDF-a and BLK CL.4 cells fibroblasts or fibroblast-like cells. Here we review the current advances on TDF, with particular focus on the structural investigation of its receptor and on its functional effects on breast and prostate cells.
I. Sokolowska A. G. Woods U. Roy C. C. Darie (&) Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY 13699-5810, USA e-mail: [email protected] M. A. Gawinowicz Protein Core Facility, College of Physicians and Surgeons, Columbia University, 160 Fort Washington Avenue, Room 415, New York, NY 10032, USA
Keywords Tumor differentiation factor Receptor Differentiation Mass spectrometry Abbreviations TDF TDF-R HBCC HPCC MCF7 cells BT-549 cells DU145 cells PC3 cells LNCaP HeLa NG108 cells BLK CL.4 cells HDF-a ORF SDS-PAGE Ab AP IAP MS ESI-MS LC–MS/MS
Tumor differentiation factor TDF-Receptor Human breast cancer cells Human prostate cancer cells Steroid-responsive breast cancer cells Steroid-resistant breast cancer cells Steroid-resistant prostate cancer cells Steroid-resistant prostate cancer cells Steroid-responsive prostate cancer cells Cervical cancer cells Mouse neuroblastoma x rat glioma cells Embryonic fibroblasts-like cells Human dermal fibroblasts Open reading frame Sodium dodecyl sulfate–polyacryl amide gel electrophoresis Antibodies Affinity chromatography Immunoaffinity purification Mass spectrometry Electrospray ionization mass spectrometry Liquid chromatography tandem mass spectrometry
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TIC m/z CID WB IF GRP78 precursor/BiP HSP8
HSP70 HSP1 HSP9
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