Chromosomal changes associated with progression of the Dunning R-3327 rat prostatic adenocarcinoma system.
Several distinct sublines have developed upon serial passages of the original Dunning R-3327-H rat prostatic tumor. These tumors, each in different progressional stages, have been examined cytogenetically in the present study in order to explore the role of chromosomal changes in tumorigenesis. The original parent H tumor, from which all the other tumors were derived, has a normal karyotype, suggesting that visible alterations in chromosome structure are not essential in the early stages of the tumor. Nonrandom involvement of chromosome 4 in abnormalities observed in the increasingly aberrant tumors derived from the H tumor indicates that chromosomes most often affected may carry genetic material which is important in the regulation of cell proliferation and that this genetic material needs to undergo changes in the process of malignant transformation. Cytogenetic analysis of the Dunning sublines as a group indicated that the karyotypes of the tumors in later progressional stages tend to deviate more from the normal than those found in earlier stages. Comparison of chromosomal changes and phenotypic characteristics observed in this series of tumors suggested that the growth rate, dedifferentiation, and attainment of metastatic ability were related to the chromosome variation. The appearance and clonal development of tumor cells with a typical translocation, i.e. t(4;7), accelerated tumor growth rates of the differentiated tumors. Duplication of chromosomes was associated with a markedly increased growth rate and dedifferentiation of tumor cells in the anaplastic tumors. In addition, chromosomal loss from tetraploidy and development of complex rearrangements were associated with attainment of metastatic ability. These results point to the importance of chromosome changes in the development and biology of tumors.
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D007621:Karyotyping; D008297:Male; D009374:Neoplasms, Experimental / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D051381:Rats