A model to study c-myc and v-H-ras induced prostate cancer progression in the Copenhagen rat

Normal rat prostate epithelial cells (EPYP-1) were isolated and immortalized with the Simian Virus-40 (SV40) large T-antigen, and transfected with the v-H-ras (EPYP-1-ras) and the c-myc oncogenes (EPYP-1-myc; EPYP-1-ras-myc) to serially create a step-wise model of tumor development in the rat prosta...

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Bibliographic Details
Published inCellular and molecular biology (Noisy-le-Grand, France) Vol. 44; no. 6; p. 949
Main Authors Lehr, J E, Pienta, K J, Yamazaki, K, Pilat, M J
Format Journal Article
LanguageEnglish
Published France 01.09.1998
Subjects
Animals
Carcinogenicity Tests
Cell Division - genetics
Cell Transplantation
Epithelial Cells - pathology
Gene Expression Regulation, Neoplastic
Genes, myc
Genes, ras
Immunohistochemistry
Keratins - metabolism
Male
Mice
Mice, Nude
Neoplasm Transplantation
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Rats
Tumor Cells, Cultured
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Summary:Normal rat prostate epithelial cells (EPYP-1) were isolated and immortalized with the Simian Virus-40 (SV40) large T-antigen, and transfected with the v-H-ras (EPYP-1-ras) and the c-myc oncogenes (EPYP-1-myc; EPYP-1-ras-myc) to serially create a step-wise model of tumor development in the rat prostate. Pronounced morphological differences were observed between EPYP-1 and the transfected sublines. The immortal epithelial cells (EPYP-1) maintained a cuboidal shape with orderly, contact mediated inhibition of growth. Oncogene transfected clones displayed a spindle shaped structure with multiple overlapping pseudopodia. Transfected cells also exhibited a greater degree of dysplasia, loss of contact inhibition growth and the upregulation of an epithelial tumor marker, cytokeratin-18. All cells exhibited anchorage independent and androgen independent growth. In vivo, EPYP-1 cells and EPYP-1-myc and formed slowly growing non-metastatic, benign tumors in immune compromised mice, while EPYP-1-ras and EPYP-1-ras-myc transfected cells produced rapidly growing, malignant tumors in similar animals. This model augments the hypothesis that tumor initiation and progression can be caused by as few as two discrete genetic events. In addition, the "normal" rat prostate epithelium and transfected daughter cell lines represent a tumor model system with distinct, well understood genetic alterations: activation of ras and myc. This model will be a valuable addition to the current cell lines used in the investigation of prostate cancer carcinogenesis.
ISSN:0145-5680