Tumor growth following genetic modifications of mouse prostate tumor cells

Abstract

Abstract Objectives 1) To determine the growth features of MyC-CaP mouse prostate tumors induced in immunodeficient nude mice and in immunocompetent FVB mice; and 2) To assess growth characteristics of MyC-CaP-p53 null tumor cells in vitro. Methods MyC-CaP cells were transfected with enhanced green fluorescent protein (eGFP), and the MyC-CaP-eGFP cells were injected intraperitoneally into naive immunodeficient nude recipients and into naive immunocompetetent FVB recipients. The transplanted tumor cells were subsequently tracked by fluorescent stereo microscopy. MyC-CaP-p53 null tumor cells were generated by inducible CRISPR/Caspase-9 gene deletion targeted to the native mutated p53 tumor suppressor gene. Results 1) Increased growth of MyC-CaP-eGFP tumors occurred in immunodeficient nude mice compared to growth in immunocompetent FVB mice; 2) decreased metastasis of MyC-CaP-eGFP tumors compared to MyC-CaP tumors occurred following injection into immunocompetent FVB mice; and 3) MyC-CaP-p53 null cells showed reduced proliferation and growth in vitro compared to non-modified MyC-CaP tumor cells. Conclusions Three conclusions can be drawn from these studies: 1) Injection of MyC-CaP-eGFP tumor cells into naive immunodeficient nude recipients allowed for adequate examination of initial tumor viability and subsequent tumor growth and metastasis; 2) Decreased MyC-CaP-eGFP tumor growth in immunocompetent FVB mice compared to immunodeficient nude mice indicates that an immune response to the eGFP protein inhibited growth of the MyC-CaP-eGFP tumor; and 3) The growth inhibition following deletion of the mutated p53 tumor suppressor gene in MyC-CaP tumor cells indicates that the mutated allele helps drive the malignancy.