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Published on: March 22, 2012
Characterization of tumor differentiation factor (TDF) and its receptor (TDF-R)
Izabela Sokolowska1, Alisa G Woods, Mary Ann Gawinowicz
1Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY 13699-5810, USA.
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.
Insights
Tumor differentiation factor (TDF), a pituitary protein, targets breast and prostate cells. Researchers identified Heat Shock 70-kDa proteins (HSP70) as potential TDF receptors, advancing understanding of TDF's endocrine function.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Tumor differentiation factor (TDF) is a pituitary-derived protein with an unclear function.
- TDF is secreted into circulation, targeting breast and prostate tissues, indicating endocrine activity.
- Previous studies identified TDF's differentiation effects on mammary and prostate cancer cells.
Purpose of the Study:
- To review current advancements in TDF research.
- To focus on the structural investigation of the TDF receptor (TDF-R).
- To elucidate TDF's functional effects on breast and prostate cancer cells.
Main Methods:
- Expression cloning was used to isolate the TDF-encoding cDNA.
- In vitro and in vivo studies assessed TDF's differentiation activity on cancer cell lines.
- Heat Shock 70-kDa proteins (HSP70) were identified as potential TDF-R candidates in breast and prostate cancer cells.
Main Results:
- TDF exhibits differentiation activity on MCF7 breast and DU145 prostate cancer cells.
- Members of the HSP70 family were identified as potential TDF receptors in multiple human breast and prostate cancer cell lines.
- HSP70 was not detected as a TDF-R in non-target cell types like HeLa or fibroblasts.
Conclusions:
- HSP70 family members are implicated as receptors for TDF in breast and prostate cancer.
- This finding provides a foundation for understanding TDF's mechanism of action.
- Further structural investigation of TDF-R is warranted to fully understand TDF's role in endocrine function and cancer cell differentiation.
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