Review

Cellular and Molecular Life Sciences

, Volume 70, Issue 16, pp 2835-2848

Characterization of tumor differentiation factor (TDF) and its receptor (TDF-R)

  • Izabela SokolowskaAffiliated withBiochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University
  • , Alisa G. WoodsAffiliated withBiochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University
  • , Mary Ann GawinowiczAffiliated withProtein Core Facility, College of Physicians and Surgeons, Columbia University
  • , Urmi RoyAffiliated withBiochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University
  • , Costel C. DarieAffiliated withBiochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University Email author 

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Abstract

Tumor differentiation factor (TDF) is an under-investigated 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.

Keywords

Tumor differentiation factor Receptor Differentiation Mass spectrometry