Loss of receptors for transforming growth factor β in human T-cell malignancies Journal Article
| Authors: | Kadin, M. E.; Cavaille-Coll, M. W.; Gertz, R.; Massagué, J.; Cheifetz, S.; George, D. |
| Article Title: | Loss of receptors for transforming growth factor β in human T-cell malignancies |
| Abstract: | Ki-1 (CD30)+ cutaneous T-cell lymphomas (CTCLs) are slowly progressive lymphomas in which initial spontaneous regression is often observed. To better understand the mechanisms of spontaneous regression and eventual tumor progression in Ki-1+ CTCLs, type β transforming growth factor (TGF-β)- mediated growth inhibition of clonally related cell lines derived from two time points, before and after tumor progression, was studied. TGF-β1 inhibited colony-forming efficiency (CFE) of a cell line (Mac-1) derived from clinically indolent Ki-1+ CTCLs but failed to inhibit CFE of Mac-2A and -2B cell lines from advanced CTCLs. To determine the basis for TGF-β1 resistance in advanced CTCL cells, we looked for possible defects in the expression of cell surface TGF-β receptors. Mac-1 cells were found to express TGF-β receptors I and II, which mediate growth inhibition, and the TGF-β-binding proteoglycan betaglycan. In contrast, receptors I and II were not detected in CTCL lines Mac-2A and -2B even though these cell lines did express betaglycan. Various treatments that unmask or induce TGF-β receptors in other cells failed to show evidence for these receptors in advanced CTCL cells. Loss of TGF-β receptor expression in these cells correlated with a marked decrease in TGF-β receptor II mRNA levels. Loss of cell surface TGF- β receptors was also found in two of five other patients with T-cell lymphomas including the Sezary syndrome and a noncutaneous T-cell lymphoma, suggesting that loss of TGF-β receptor expression may be a recurrent feature of human T-cell malignancies. |
| Keywords: | adult; human cell; case report; comparative study; t-lymphocytes; transforming growth factor beta; cell line; tumor cells, cultured; skin; cancer regression; t cell lymphoma; lymphoma, t-cell; molecular sequence data; receptors, transforming growth factor beta; base sequence; tumor growth; tumor suppressor genes; blotting, northern; skin lymphoma; growth inhibitors; sezary syndrome; growth factor receptor; tumor stem cell assay; lymphoma, t-cell, cutaneous; messenger rna synthesis; lymphomatoid papulosis; human; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; growth factor receptors |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 91 |
| Issue: | 13 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1994-06-21 |
| Start Page: | 6002 |
| End Page: | 6006 |
| Language: | English |
| DOI: | 10.1073/pnas.91.13.6002 |
| PROVIDER: | scopus |
| PMCID: | PMC44125 |
| PUBMED: | 8016105 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: PNASA C2 -- Source: Scopus |
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