Autocrine growth stimulation by transforming growth factor-alpha in human non-small cell lung cancer
| Autor: | P. A. Steck, A. F. Gazdar, N. Yen, G. E. Gallick, Jack A. Roth, Elizabeth A. Putnam, Kang Fang, B. Akpakip |
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| Rok vydání: | 1992 |
| Předmět: |
TGF alpha
Lung Neoplasms Mice Nude Suramin Mice Radioligand Assay Carcinoma Non-Small-Cell Lung Tumor Cells Cultured Animals Humans Growth factor receptor inhibitor RNA Neoplasm Autocrine signalling Tumor Stem Cell Assay biology Dose-Response Relationship Drug Cell growth Transforming Growth Factor alpha Molecular biology Recombinant Proteins ErbB Receptors Oncology Cell culture biology.protein Surgery A431 cells Platelet-derived growth factor receptor Neoplasm Transplantation Transforming growth factor |
| Zdroj: | Surgical oncology. 1(1) |
| ISSN: | 0960-7404 |
| Popis: | We studied the biological response to and production of transforming growth factor-alpha (TGF-alpha) by the non-small cell lung carcinoma (NSCLC) clonal cell lines H226b, H322a, H460a, H596b. Each of these cell lines expressed epidermal growth factor receptor (EGFR) as determined by [125I]EGF competitive binding and Scatchard analysis and by phosphorylation. The receptors were functionally active as determined in immune complex kinase assays. H322a, H226b, H460a, and H596b cells showed stimulated [3H]thymidine (Thd) uptake in response to TGF-alpha. Exogenously added TGF-alpha increased colony formation in soft agar for three of the cell lines in media containing serum. All cell lines expressed TGF-alpha detected by immunohistochemistry and TGF-alpha mRNA, although to differing degrees. Cell lysates and spent media competed for EGFR binding with EGF, thus demonstrating production of TGF-alpha-like activity. The anti-TGF-alpha monoclonal antibody AB-3 inhibited the uptake of [3H]Thd by proliferating H322a and H226b cells but not H460a and H596b cells. No inhibition occurred with MOPC21 antibody and inhibition was completely reversed by addition of TGF-alpha to the culture. Suramin inhibited cell proliferation and [3H]Thd uptake by all cell lines. Inhibition of H460a and H596b cells was reversed with exogenous TGF-alpha but not PDGF. Our data suggests that TGF-alpha is a mediator of autocrine growth stimulation for NSCLC cells, and that for some NSCLC cells cytoplasmic binding of receptor and ligand is the primary mechanism for autocrine growth stimulation. |
| Databáze: | OpenAIRE |
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