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Expression of the metastatic phenotype in cells transfected with human metastatic tumor DNA
Abstract:
NIH 3T3 mouse fibroblasts form nonmetastasizing fibrosarcomas upon transformation by the Ha-ras oncogene isolated from the EJ human bladder carcinoma cell line and subcutaneous inoculation into immunocompetent NFS/NCr mice. DNA from a human metastatic tumor was transfected into these Ha-ras transformants, and one of the resulting colonies yielded a lung metastasis after subcutaneous inoculation. DNA was isolated from this metastasis and subjected to a second round of transfer into Ha-ras-transformed NIH 3T3 cells. Inoculation of these transfected cultures into mice led once again to formation of metastases, this time at a higher frequency. Examination of four of the resulting metastases revealed discrete human DNA fragments that were common to all four. These findings demonstrate that the metastatic phenotype can be transferred via DNA from cell to cell and is associated with the presence of a discrete DNA segment. This segment is not identical to the myc oncogene or to any of the frequently detected ras tumor oncogenes.
Insights
The metastatic phenotype, the ability of cancer to spread, can be transferred between cells using DNA. This study identified a specific DNA segment linked to cancer metastasis, distinct from known oncogenes like ras or myc.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- NIH 3T3 mouse fibroblasts, when altered by the Ha-ras oncogene, form non-metastasizing fibrosarcomas.
- The Ha-ras oncogene was derived from the EJ human bladder carcinoma cell line.
Purpose of the Study:
- To investigate the genetic basis of cancer metastasis.
- To determine if the metastatic phenotype can be transferred via DNA transfection.
Main Methods:
- Transfection of DNA from a human metastatic tumor into Ha-ras-transformed NIH 3T3 cells.
- Subcutaneous inoculation of transfected cells into mice to observe metastasis formation.
- Isolation and analysis of DNA from resulting metastases to identify common genetic fragments.
Main Results:
- A single transfection event resulted in a lung metastasis.
- Subsequent DNA transfer from this metastasis led to more frequent metastatic formation.
- Common discrete human DNA fragments were identified in multiple metastases.
Conclusions:
- The metastatic phenotype is transferable via DNA, suggesting a genetic component.
- A specific DNA segment is associated with the metastatic phenotype.
- This DNA segment is not the myc oncogene or common ras oncogenes.