Oncogene induction of metastases.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Metastasis involves complex gene product interactions.
• Increased expression of specific genes can enhance tumor metastatic potential.
• The c-Ha-ras oncogene serves as a model to study metastatic gene products.

Purpose of the Study:

• To investigate the role of the c-Ha-ras oncogene in inducing the metastatic phenotype.
• To identify gene products associated with augmented metastatic potential.
• To explore factors influencing ras-induced metastasis.

Main Methods:

• Transfection of the activated ras oncogene into various fibroblast cell lines (3T3, 10T1/2, adult rat fibroblasts).
• Assessment of metastatic potential in nude mice and syngeneic recipients.
• Investigation of the effect of adenovirus 2 E1A on ras-induced metastasis.

Main Results:

• Ras oncogene transfection induced high numbers of spontaneous metastases in recipient cells.
• Ras oncogene increased the metastatic aggressiveness of low-metastatic murine tumors.
• Ras oncogene transfection led to the production of type IV collagenase, motility factors, and growth factors.
• Not all recipient cells exhibited the metastatic phenotype upon ras oncogene transfection.
• Adenovirus 2 E1A and potential natural suppressor genes inhibited ras-induced metastasis.

Conclusions:

• The ras oncogene initiates a cascade of gene functions promoting rapid progression to the metastatic phenotype.
• The mechanism involves complex interactions between the ras p21 product and cellular gene products.
• The metastatic potential induced by ras is cell-type dependent and can be modulated by other genes.