Small cell carcinoma of the lung (SCCL) is a common form of lung cancer and less than 5% of patients with this type of carcinoma survive more than five years. A major reason for the dismal prognosis with SCCL is that this tumor metastasizes early and widely. Since SCCL is an highly metastatic tumor, it was selected as an extremely appropriate prototype for determining the genetic basis for the metastatic phenotype in human cancer. The goal of this proposal is to investigate an experimental model of spontaneous metastases from subcutaneous tumors in nude mice induced by NlH/3T3 cells transfected by genomic DNA from a cell line established from metastatic human small cell carcinoma of the lung (SCCL). Metastases are rapidly produced in this model and preliminary studies indicate the presence of human sequences in the cells of the pulmonary metastases. It is hypothesized that these human sequences represent genes which are etiologically related to the metastatic phenotype expressed by these cells. It is anticipated that these investigations will provide significant amounts of important new information and provide a better understanding of the mechanisms of metastases from human malignant tumors.
The specific aims are: 1. To determine whether transfection with DNA from metastatic SCCL obtained directly from a patient will induce NIH/3T3 and normal fibroblasts to develop the metastatic phenotype. 2. To identify the human sequences present in the transfected metastatic NIH/3T3 cells and investigate their biological activity. 3. To evaluate factors which may influence the incidence of pulmonary metastases in the nude mice based upon the identification of the human sequences (gene or genes) in the metastatic cells.
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