Light microscope autoradiography was utilized to investigate the separate proliferative activities of the basal and glandular cell types during androgen-mediated restoration of the ventral prostatic epithelium in castrated rats. Our objective was to determine whether the proliferative population of the prostatic epithelium is restricted to the basal cell subtype under these experimental conditions. In the intact animal, substantial numbers of basal as well as glandular cells were found to be proliferating. The basal cell labeling index (LI) was 3.75% +/- 0.3% or 1.85 +/- 0.4 x 10(5) labeled cells per prostate. For the glandular cells the comparable figures were 0.38% and 3.32 +/- 1.5 x 10(5). Seven days after surgical castration, both subtypes persisted. However, only the numbers of glandular cells were found to be significantly reduced (66% decrease). When androgens were replaced by daily subcutaneous injection (testosterone propionate, 2 mg/0.2 ml sesame oil), both cell types responded with significantly increased proliferation. The temporal pattern of response displayed by each cell type was very similar. A greater proportion of basal than glandular cells responded, ie, 28% vs 11% LI. However, in terms of approximate numbers of cells labeled during the peak response, the value for the glandular cells was larger, ie, 2.4 vs 1.1 x 10(6) labeled cells. These data clearly indicate that under normal conditions as well as during testosterone stimulation, basal cells are not the sole population of proliferating cells in the prostatic epithelium. Thus, basal cells, as a distinct morphologic population, are not homogeneously undifferentiated stem cells which give rise to differentiated and nonproliferating glandular epithelial cells. Aspects of these data can nevertheless be interpreted to support the idea that the prostatic epithelium is maintained by a single cell lineage system in which the stem cells comprise a subpopulation of the basal cells. Alternatively, the two populations may be separate and distinct as no data are presented which unequivocally links the two cell types in a precursor-progeny relationship.
Owing to progression of the original spontaneous Dunning R-3327 rat prostatic cancer, a large series of transplantable prostatic tumors have been isolated that differ widely in their histological degree of differentiation, growth rate, androgen sensitivity, and metastatic ability. Using these parameters as criteria, the full spectrum of disease progression is represented within this Dunning system of rat prostatic cancers, ranging from slow-growing, well-differentiated, androgen-sensitive, nonmetastatic forms to fast-growing, anaplastic, androgen-independent, highly metastatic forms. Cytogenetic analysis of the two least progressionally advanced Dunning cancers (i.e., histologically well-differentiated, slow-growing, nonmetastatic variants) demonstrated no structural or numerical chromosomal aberration, suggesting that the initial development of prostatic cancer may not require detectable cytogenetic changes. In contrast, all 16 of the progressionally more advanced Dunning variants analyzed had a series of characteristic structural and/or numerical chromosomal aberrations that minimally involved chromosome 4. This nonrandom involvement of chromosome 4 was consistently observed regardless of whether the karyotype of the cancer was near-diploid or hyperaneuploid, suggesting that chromosome 4 aberrations are specifically involved in the progression of rat prostatic cancer. In addition, all four variants that were highly metastatic had, besides aberration of chromosome 4, structural aberrations involving chromosomes 1, 2, and 11. Of the 14 variants that did not have a high metastatic ability, only two had a similar aberrations involving chromosomes 1, 2, 4, and 11, suggesting that these specific chromosomal aberrations may be necessary, albeit not sufficient, for a high metastatic ability of rat prostatic cancers.
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