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Correlation between Ha-ras gene amplification and spontaneous metastasis in NIH 3T3 cells transfected with genomic DNA from human skin cancers

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Abstract

Our previous studies have shown that DNA from some human skin cancers contained activated Ha-ras oncogenes capable of inducing tumorigenic transformation when introduced into NIH 3T3 cells by DNA-mediated gene transfer. In addition, we found that NIH 3T3 cells transfected with DNA from one of the human skin cancers not only induced s.c. tumors at the site of injection but also metastasized spontaneously to the lungs in 100 per cent of nude mice injected. In this present study we examined the relationship between Ha-ras oncogene amplification and metastatic potential in tumors induced by various human skin cancer DNA-transfectants. Total cellular RNA was extracted from nude mouse tumor cell lines and analyzed by northern blot hybridization to a32P-labeled, nick-translated Ha-ras probe. The metastatic potential of nude mouse tumor cell lines was assessed by their ability to form lung colonies after i.v. or s.c. injection. It was found that only the tumors expressing high levels of Ha-ras gene transcripts induced spontaneous metastasis after s.c. injection. There appeared to be little correlation between the level of Ha-ras oncogene amplification and experimental metastasis. These results suggest that amplification and overexpression of Ha-ras oncogene may play a role in the escape of cells from the primary tumor rather than in the ability of cells to survive in the circulatory system and colonize secondary sites.

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Abbreviations

HBSS:

Hank's balanced salt solution

SSC:

Standard saline citrate

SDS:

Sodium dodecyl sulfate

s.c.:

Subcutaneous

i.v.:

Intravenous

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Authors and Affiliations

  1. Department of Immunology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 178, 77030, Houston, TX, USA

    Honnavara N. Ananthaswamy, Janet E. Price, Michael A. Tainsky, Leonard H. Goldberg & E. S. Bales

  2. Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 178, 77030, Houston, TX, USA

    Honnavara N. Ananthaswamy, Janet E. Price & Michael A. Tainsky

  3. Department of Dermatology, Baylor College of Medicine, 77030, Houston, TX, USA

    Leonard H. Goldberg

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  1. Honnavara N. Ananthaswamy
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  5. E. S. Bales
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Ananthaswamy, H.N., Price, J.E., Tainsky, M.A. et al. Correlation between Ha-ras gene amplification and spontaneous metastasis in NIH 3T3 cells transfected with genomic DNA from human skin cancers. Clin Exp Metast 7, 301–313 (1989). https://doi.org/10.1007/BF01753682

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