Serial Transplantation: A Method for Inducing Mammary Tumours in Sprague Dawley Rats

Study of breast cancer biology has been limited due to scarcity of available human samples, cost and preservation of cell lines thus, necessitating the use of chemically-induced rodent models. This study defines a protocol demonstrating that serial transplants obtained from 7,12-DMBA-induced mammary tumours had ability to generate and propagate mammary tumour cells with shorter latency. It also compared the changes in morphology and gene expression in the primary tumour cells and serial transplants. Virgin 50-day old female Sprague-Dawley rats were administered 10 mg/kg DMBA sub-dermally. Primary tumours were harvested, half processed for histology while the remainder was processed as a cell suspension and transplanted into clean rats. Five percent (5%) of rats developed multiple mammary carcinoma after DMBA injection with a latency of 112 days. However, 35% and 56% developed mammary tumours in the first and second transplants with mean latency of 18 and 9 days respectively. This protocol induced significant palpable tumour response as well as reduced expression of ER and PR in the serial transplants as compared to the primary tumours while HER2 was undetectable in all tumours. Morphologically, tumours were carcinomas having different levels of differentiation: primary tumours showed moderate differentiation, first transplant showed poor differentiation and second transplant showed well-differentiated carcinomas. It can be concluded that serial transplants can continuously generate and propagate mammary tumour cells in shorter time periods while losing their ER and PR dependence. This could provide a useful tool for testing of therapeutic drugs for breast cancer particularly in developing economies.

Key Words: Serial transplantation, immunohistochemistry, estrogen receptors, progesterone receptors