Cellular and Molecular Life Sciences

, Volume 70, Issue 16, pp 2835–2848 | Cite as

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

  • Izabela Sokolowska
  • Alisa G. Woods
  • Mary Ann Gawinowicz
  • Urmi Roy
  • Costel C. Darie
Review

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 

Abbreviations

TDF

Tumor differentiation factor

TDF-R

TDF-Receptor

HBCC

Human breast cancer cells

HPCC

Human prostate cancer cells

MCF7 cells

Steroid-responsive breast cancer cells

BT-549 cells

Steroid-resistant breast cancer cells

DU145 cells

Steroid-resistant prostate cancer cells

PC3 cells

Steroid-resistant prostate cancer cells

LNCaP

Steroid-responsive prostate cancer cells

HeLa

Cervical cancer cells

NG108 cells

Mouse neuroblastoma x rat glioma cells

BLK CL.4 cells

Embryonic fibroblasts-like cells

HDF-a

Human dermal fibroblasts

ORF

Open reading frame

SDS-PAGE

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

Ab

Antibodies

AP

Affinity chromatography

IAP

Immunoaffinity purification

MS

Mass spectrometry

ESI-MS

Electrospray ionization mass spectrometry

LC–MS/MS

Liquid chromatography tandem mass spectrometry

TIC

Total ion current

m/z

Mass/charge

CID

Collision-induced dissociation

WB

Western blotting

IF

Immunofluorescence

GRP78 precursor/BiP

Glucose regulated protein (accession # gi6470150/gi386758)

HSP8

Heat shock 70-kDa protein 8 isoform 1 (accession # gi62897129/gi5729877)

HSP70

Heat shock 70-kDa protein (accession # gi386785)

HSP1

Heat shock 70-kDa protein 1 (accession # gi4529893)

HSP90Bb

Heat shock 90Bb protein (accession # gi20149594)

HSP90

Heat shock protein 90 (accession # gi306891)

HSPA9

Heat shock 70-kDa protein 9 (accession # gi12653415)

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Copyright information

© Springer Basel 2012

Authors and Affiliations

  • Izabela Sokolowska
    • 1
  • Alisa G. Woods
    • 1
  • Mary Ann Gawinowicz
    • 2
  • Urmi Roy
    • 1
  • Costel C. Darie
    • 1
  1. 1.Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular ScienceClarkson UniversityPotsdamUSA
  2. 2.Protein Core Facility, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

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