J Korean Cancer Assoc.
2000 Jun;32(3):619-628.
Regulation of Gene Expression in Murine Renal Cell Carcinoma Cells
Growing in Ectopic or Orthotopic Organs of Syngenic Mice
- Affiliations
-
- 1Cancer Research Center, Center for Clinical Research, Samsung Biomedical Research Institute.
- 2Departments of Thoracic Surgery, Sungkyunkwan University
School of Medicine, Seoul, Korea.
- 3Departments of Internal Medicine, Sungkyunkwan University
School of Medicine, Seoul, Korea.
Abstract
-
PURPOSE: The biologic behavior of tumor cells is partially controlled by the microenvironment.
We investigated the expression levels of several genes involved in metastasis and drug response
in RENCA cells growing in ectopic (skin) and orthotopic (kidney) sites.
MATERIALS AND METHODS
Murine renal carcinoma cells were injected into kidney (orthotopic)
and subcutis (ectopic) of syngeneic mice. Mice were treated with doxorubicin (DXR) (8 mg/kg)
on days 8 and 15 after tumor cell implantation. Drug response was measured both in vivo and
ex vivo by measuring tumor size and MTT assay. We also performed an in situ mRNA
hybridization to estimate the expression levels of mdr (multidrug resistance), EGFR (epidermal
growth factor receptor) and type IV collagenase.
RESULTS
RENCA cells growing in the kidney of syngeneic mice produced metastatic lesions in
the lung (57% of mice), while the same cells growing in the subcutis did not. Tumors growing
in the kidney were more resistant to DXR than tumors growing in the subcutis. MTT assays
revealed that tumor cells derived from kidney were more resistant to DXR than those cells from
subcutis. In situ hybridization analyses showed that transcripts of EGFR and type IV collagenase
genes in kidney tumors were higher than those of subcutaneous tumors but mdr expression
showed no difference between the two tumors.
CONCLUSION
These results demonstrate that the organ environment influences the drug responsive
ness and the expression of EGFR and type IV collagenase genes in murine renal cell carcinoma
cells.