Prostate Carcinogenesis in the AXC Rat

Shain, Sydney A.; McCullough, B. D.; Nitchuk, M.; Boesel, Robert W.

doi:10.1159/000225203

Cited by 30 publications

(12 citation statements)

References 13 publications

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“…Ventral and dorsolateral prostate nuclear androgen receptors evidenced a 35-50% aging-associated decrease in both breeds of rats (19). Additionally, we have identified spontaneous adenocarcinomas ofthe AXC rat ventral prostate, whereas this lesion was not found in the rat dorsolateral prostate (22,25). The incidence of this adenocarcinoma was 70% in AXC rats >30 mo of age (25).…”

Section: Resultsmentioning

confidence: 76%

“…Additionally, we have identified spontaneous adenocarcinomas ofthe AXC rat ventral prostate, whereas this lesion was not found in the rat dorsolateral prostate (22,25). The incidence of this adenocarcinoma was 70% in AXC rats >30 mo of age (25). It is interesting to speculate that the high incidence of prostatic hyperplasia and low incidence of adenocarcinoma of the prostate of the aging canine as compared to the absence of hyperplasia and high incidence of adenocarcinoma of the ventral prostate of the aging AXC rat is in some manner related to altered hormonal regulation of cell function which is reflected in the different relationship between aging and prostatic androgen receptor content in these two species.…”

Section: Resultsmentioning

confidence: 81%

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Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate

Shain¹,

Boesel²

1978

J. Clin. Invest.

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A B S -R A C T A procedure was developed for rneeasurement of androgeni receptors in cytoplasmic extracts of prostates froms intact dogs. The protocol utilized exchange saturatioin analysis at 15°C employing the synthetic androgen R1881 (17,8-hydroxy-17an-methylestra-4,9, 1 1-trien-3-one) as the ligand probe anid quantitatively dletected total cytoplasmic androgeni receptor (R, anidrogen-free receptor, and R,.A, androgenoccupied receptor) present at the initiation of the assay. This protocol was employed in conjunctioni with a tissue mince saturation anialysis procedure (for (uantitation of nuclear androgen receptor) to (quanititate total androgeni receptor content of normal and hyperplastic prostates obtained fromi young (2.5-or 4.6-yr old) and aged (12.5-yr old) purebred dogs of known birth date.The total cytoplasmic androgeni receptor content (piconmoles per prostate) of hyperplastic prostates was 4.6-fold greater than that of normal prostates. The total nuclear androgen receptor content of hyperplastic prostates (piconmoles per prostate meassured in crude nuclear preparations) was either 5.0-(4.6-yr-old dogs) or 7.8-fold (2.5-yr-old dogs) greater than that of normnal prostates. However, androgen receptor content per cell was identical for hyperplastic and normal canine prostates, with the exception that nuclear androgeni receptor was diminished in prostates fromii 2.5-yr-old dogs. The the molecular mlechanismiis of hornmone action have led to an increasing number of investigations of hormonal regulationi of caniine prostate functioni (4-10). Although histologic features (11) and hormone sensitivity (3,4,(12)(13)(14) of the two prostatic hyperplasias differ, the induction of canine prostatic hyperplasia by injection of anidrostaniediol' or anidrostanediol plus 17,8-estradiol (9) suipports the use of the caniine model for studies of pathogenesis. When compared to normal prostates, 1)oth humilan anid caninle prostatic hyperplasia are characterized by an approximately fivefold increase (7,15) in the conicentrationi of the prostatic androgen 5a-dihydrotestosterone (16). However, the rate of conversion of testosterone to 5a-dihydrotestosterone is not significantly different for normal and hyperplastic prostates of either specie (7, 15). The observations suiggest that an alteration in the mechanism of 5a-dlihydrotestosterone accumulation may be related to the pathogen esis of prostatic hyperplasia.Current concepts of the mechanism of steroid hormone regulationi of cell function envisions a process whereby effector steroid initially interacts with cytoplasmic receptor proteins. The highly steroid specific b)inding of effector to cytoplasmic receptor protein promotes translocationi of the receptor-steroid complex into the nuclear compartment (17,18). Consequently, the capacity of the prostate to specifically accumulate 5a-dihydrotestosterone (effector steroid) would be expected to be related to the tissue cointenit of cytoplasmic and nuclear androgen receptor. As part of a study of aging-associated changes in st...

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 81%

Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate

Shain¹,

Boesel²

1978

J. Clin. Invest.

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“…Autopsy studies indicate that prostate cancer incidence approaches 60–70% in the 8th and 9th decade of life [12], [13]. A relationship between aging and inflammation, hyperplasia and neoplasia of prostatic tissue has also been observed in rodents and dogs [14], [15], [16], [17]. Overall, the etiology of these diseases remains poorly defined despite causing substantial morbidity and mortality in the population.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

et al. 2010

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BackgroundAdvancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate gland including benign prostatic hyperplasia (BPH) and prostate carcinoma. The prostate is comprised of a functional secretory epithelium, a basal epithelium, and a supporting stroma comprised of structural elements, and a spectrum of cell types that includes smooth muscle cells, fibroblasts, and inflammatory cells. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stroma could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate microenvironment that could influence pathology.Methodology/Principal FindingsWe quantitated transcript levels in microdissected glandular-adjacent stroma from young (age 4 months) and old (age 20–24 months) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding proteins associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/oxidative stress (e.g., Apod, Serpinb5) and other paracrine-acting effects (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age-associated declines. By histology, immunofluorescence, and electron microscopy we determined that the collagen matrix is abundant and disorganized, smooth muscle cell orientation is disordered, and inflammatory infiltrates are significantly increased, and are comprised of macrophages, T cells and, to a lesser extent, B cells.Conclusion/SignificanceThese findings demonstrate that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate.

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“…It is interesting to note that the R 3327 tumor in the Copenhagen rat originated in the dorsal lobe of the prostate which is devoid of cRABP as shown here and has decreased levels of androgen receptor (Table I). In the ACI rat [33,40] prostatic adenocarcinomas originate in the ventral lobe of the prostate in a background of agingassociated decrease in androgen receptor content and androgen dependence [32]. In the Wistar germfree rats the prostatic lobe of origin of various spontaneous tumors has not been determined [26], but a marked reduction in androgen receptor content occurs in the ventral, and lateral prostatic lobes of aging Wistar rats, whereas no significant change occurs in the dorsal lobe [27].…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid binding protein in normal and neoplastic rat prostate

Gesell

Brandes

Arnold³

et al. 1982

The Prostate

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Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.

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Prostate Carcinogenesis in the AXC Rat

Cited by 30 publications

References 13 publications

Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate

Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

Retinoic acid binding protein in normal and neoplastic rat prostate

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