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Arguments against the prostatic origin of the R-3327 Dunning H tumor

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Virchows Archiv B

Summary

The Dunning tumor, originally described as a carcinoma of the rat dorsal prostate, has for long been used as an experimental model of prostatic cancer. We have recently presented a number of morphological findings that are incompatible with the prostatic origin of the H-subline of the Dunning tumor. In this paper, biochemical and immunohistochemical markers of rat prostate and mammary gland are studied in the R-3327 Dunning H tumor. Pieces of the H tumor were inoculated in male or lactating female rats. The electrophoretic protein pattern of Dunning tumor extracts was more similar to that of the mammary gland than the dorsolateral prostate. Proteins selectively appearing after metabolic labeling in Dunning tumors grown in lactating rats corresponded to labeled proteins in mammary glands from the same animals. Secretory proteins typical of the lateral prostate (SVS II) and dorsal prostate (transglutaminase) could not be detected immunohistochemically in the Dunning tumor. Western blot studies of tumor extracts and slot blot analysis of RNA preparations from the tumor confirmed the absence of SVS II and prostate specific transglutaminase from the Dunning tumor. On the other hand, the presence of mammary gland proteins such as milk fat globule membrane proteins, lactoperoxidase and lactalbumin were detected in the Dunning tumor by immunohistochemistry and Western blotting, but were absent from the dorsolateral prostate. Transferrin-mRNA, expressed in the male urogenital tract and also in the liver and other tissues, was detected in the mammary gland and Dunning tumor, but not in the dorsolateral prostate. The absence of mammary gland secretory β-casein in the Dunning tumor was related to the elevated Ha-ras oncogene expression in the tumor, previously reported to suppress casein expression. The findings clearly demonstrate that the prostate cannot be the origin of the Dunning tumor, presently being used in prostatic cancer research. The designation prostatic adenocarcinoma for this tumor is therefore invalid. Furthermore, the data support our view that mammary gland might be the origin of the Dunning tumor, although the derivation from the bulbourethral or the parotid glands cannot strictly be excluded.

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Abbreviations

AA:

acrylamide

ABC:

avidin-biotin-peroxidase complex

BSA:

bovine serum albumine

bp:

base pairs

CsTFA:

cesium trifluoroacetate

kD:

kilo Dalton (Mr)

MFGM:

milk fat globule membrane proteins

PAP complex:

peroxidase anti-peroxidase complex for immunodetection

PAP line:

tumor line of the Dunning tumor

PBS:

phosphate buffered saline (149 mM NaCl, 2.2 mM KH2PO4, 99 mM Na2HPO4, pH 7.4)

PMSF:

phenylmethylsulfonylfluoride

PAGE:

polyacrylamide gelelectrophoresis

PBP:

Prostatic Binding Protein

SDS:

sodium dodecylsulfate

SSC:

standard sodium citrate (150 mM NaCl, 15 mMsodium citrate pH 7.0)

SVS II:

seminal vesicle protein II

TCA:

trichloroacetic acid

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Philipps-Universität, Robert-Koch-Strasse 6, W-3550, Marburg, Federal Republic of Germany

    Heinz-Werner Goebel, Ulrich Rausch, Martin Steinhoff, Jürgen Seitz, Michael Bacher & Gerhard Aumüller

  2. Dipartimento di Scienze Biomediche e, Oncologia Umana University of Torino, 1-10126, Torino, Italy

    Mauro Papotti & Gianni Bussolati

  3. Department of Biomedical Sciences, University of Tampere, SF-33101, Tampere, Finland

    Pentti Tuohimaa

Authors
  1. Heinz-Werner Goebel
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  2. Ulrich Rausch
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  3. Martin Steinhoff
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  4. Jürgen Seitz
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  5. Michael Bacher
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  6. Mauro Papotti
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  7. Gianni Bussolati
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  8. Pentti Tuohimaa
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  9. Gerhard Aumüller
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Additional information

This research was founded by the Deutsche Krebshilfe, grant W 6/90/Au 1 (G.A.)

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Goebel, HW., Rausch, U., Steinhoff, M. et al. Arguments against the prostatic origin of the R-3327 Dunning H tumor. Virchows Archiv B Cell Pathol 62, 9–18 (1992). https://doi.org/10.1007/BF02899660

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  • DOI: https://doi.org/10.1007/BF02899660

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