Reverse transformation of multidrug-resistant cells Journal Article
| Authors: | Biedler, J. L.; Spengler, B. A. |
| Article Title: | Reverse transformation of multidrug-resistant cells |
| Abstract: | Spontaneously transformed Chinese hamster lung cells with high levels of resistance (≈ 100-fold to 70,000-fold) to actinomycin D, daunorubicin, or vincristine exhibit morphology and growth patterns characteristic of normal cells in vitro and reduced tumorigenicity in vivo. These reverse transformed, multidrug-resistant cells amplify and highly overexpress one or more genes encoding P-glycoprotein. Similarly, hydrocarbon-induced mouse sarcoma cells selected with actinomycin D, vincristine, or ethidium bromide developed high levels of resistance associated with reduced drug accumulation and suppression of malignancy. To determine whether human tumor cells would undergo similar changes and whether reverse transformation reflected an altered state of differentiation, nine multidrug-resistant sublines were selected with four agents from human neuroblastoma cells with well defined pathways of differentiation. Those five with resistance levels above about 125-fold showed a reduced tumor frequency as compared to control cells. All resistant sublines showed altered differentiation. The changes in transformation phenotype appear to be intrinsic and not the result of altered immunogenicity. Two additional consequences of high level multidrug resistance have been observed: change in ganglioside composition in the Chinese hamster cells, manifested as a block in higher ganglioside biosynthesis and/or a relative increase in GM3, and increase in epidermal growth factor receptor in all three cell systems. A tentative hypothesis links ganglioside and growth factor receptor changes to the change in transformation phenotype. The basis of the reverse transformation phenomenon is not known, but the major alterations in expression of P-glycoprotein, gangliosides, and the epidermal growth factor receptor implicate, in some way, the plasma membrane. © 1994 Kluwer Academic Publishers. |
| Keywords: | controlled study; review; cancer growth; nonhuman; antineoplastic agents; comparative study; animal cell; animal; mice; cell structure; tumor differentiation; cancer cell culture; tumor cells, cultured; neuroblastoma; neuroblastoma cell; protein synthesis; cell transformation; cell membrane; ganglioside gm3; multidrug resistance; differentiation; drug resistance, multiple; cricetulus; gangliosides; glycoprotein p; sarcoma cell; sarcoma, experimental; transformation, genetic; tumorigenicity; egf receptor; human; priority journal; support, u.s. gov't, p.h.s.; hamsters; reverse transformation |
| Journal Title: | Cancer and Metastasis Reviews |
| Volume: | 13 |
| Issue: | 2 |
| ISSN: | 0167-7659 |
| Publisher: | Springer |
| Date Published: | 1994-06-01 |
| Start Page: | 191 |
| End Page: | 207 |
| Language: | English |
| DOI: | 10.1007/bf00689636 |
| PROVIDER: | scopus |
| PUBMED: | 7923550 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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