Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms

D. L. Schaffner, R. Barrios, M. R. Shaker, S. Rajagopalan, S. L. Huang, D. J. Tindall, C. Y F Young, P. A. Overbeek, R. M. Lebovitz, M. W. Lieberman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND: Although prostate cancer is one of the most prevalent tumors in men, knowledge of its biology has been hindered by lack of animal models. We have attempted to develop a prostate cancer model utilizing transgenic mouse technology. EXPERIMENTAL DESIGN: Two lines of transgenic mice were derived from one cell stage embryos injected with a fusion gene consisting of a mutated (codon 12) ras gene driven by the human prostate specific antigen (PSA) promoter in an attempt to target the oncogene specifically to the mouse prostate gland. Nontransgenic FVB/N mice were used as controls. The animals were sacrificed for study between 4 and 55 weeks of age. RESULTS: All organs were normal except the salivary glands and gastrointestinal tracts, both of which developed carcinomas in animals older than 44 weeks. The salivary gland tumors were of ductal origin, exhibited a variable degree of differentiation, and were shown to contain abundant PSAras mRNA by in situ hybridization. The gastrointestinal tract tumors were undifferentiated but appeared to be of stromal origin. Both salivary gland and gastrointestinal tumors occasionally metastasized. No transgene expression could be demonstrated in the prostate gland by either reverse transcription-polymerase chain reaction or in situ hybridization. CONCLUSIONS: Lack of transgene expression by the prostate can be explained on the basis of the apparent species specificity previously observed for PSA. Expression in salivary gland is best attributed to identity between the nucleotide sequences of the PSA promoter and of a mouse glandular kallikrein normally secreted by the salivary gland.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalLaboratory Investigation
Volume72
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Gastrointestinal Neoplasms
Salivary Glands
Transgenic Mice
Gastrointestinal Tract
Prostate
Prostate-Specific Antigen
Transgenes
Genes
In Situ Hybridization
Prostatic Neoplasms
Tissue Kallikreins
Species Specificity
Neoplasms
Glandular and Epithelial Neoplasms
ras Genes
Gene Fusion
Oncogenes
Codon
Reverse Transcription
Embryonic Structures

Keywords

  • Prostate-specific antigen
  • ras

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Schaffner, D. L., Barrios, R., Shaker, M. R., Rajagopalan, S., Huang, S. L., Tindall, D. J., ... Lieberman, M. W. (1995). Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms. Laboratory Investigation, 72(3), 283-290.

Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms. / Schaffner, D. L.; Barrios, R.; Shaker, M. R.; Rajagopalan, S.; Huang, S. L.; Tindall, D. J.; Young, C. Y F; Overbeek, P. A.; Lebovitz, R. M.; Lieberman, M. W.

In: Laboratory Investigation, Vol. 72, No. 3, 1995, p. 283-290.

Research output: Contribution to journalArticle

Schaffner, DL, Barrios, R, Shaker, MR, Rajagopalan, S, Huang, SL, Tindall, DJ, Young, CYF, Overbeek, PA, Lebovitz, RM & Lieberman, MW 1995, 'Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms', Laboratory Investigation, vol. 72, no. 3, pp. 283-290.
Schaffner DL, Barrios R, Shaker MR, Rajagopalan S, Huang SL, Tindall DJ et al. Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms. Laboratory Investigation. 1995;72(3):283-290.
Schaffner, D. L. ; Barrios, R. ; Shaker, M. R. ; Rajagopalan, S. ; Huang, S. L. ; Tindall, D. J. ; Young, C. Y F ; Overbeek, P. A. ; Lebovitz, R. M. ; Lieberman, M. W. / Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms. In: Laboratory Investigation. 1995 ; Vol. 72, No. 3. pp. 283-290.
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AU - Tindall, D. J.

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AB - BACKGROUND: Although prostate cancer is one of the most prevalent tumors in men, knowledge of its biology has been hindered by lack of animal models. We have attempted to develop a prostate cancer model utilizing transgenic mouse technology. EXPERIMENTAL DESIGN: Two lines of transgenic mice were derived from one cell stage embryos injected with a fusion gene consisting of a mutated (codon 12) ras gene driven by the human prostate specific antigen (PSA) promoter in an attempt to target the oncogene specifically to the mouse prostate gland. Nontransgenic FVB/N mice were used as controls. The animals were sacrificed for study between 4 and 55 weeks of age. RESULTS: All organs were normal except the salivary glands and gastrointestinal tracts, both of which developed carcinomas in animals older than 44 weeks. The salivary gland tumors were of ductal origin, exhibited a variable degree of differentiation, and were shown to contain abundant PSAras mRNA by in situ hybridization. The gastrointestinal tract tumors were undifferentiated but appeared to be of stromal origin. Both salivary gland and gastrointestinal tumors occasionally metastasized. No transgene expression could be demonstrated in the prostate gland by either reverse transcription-polymerase chain reaction or in situ hybridization. CONCLUSIONS: Lack of transgene expression by the prostate can be explained on the basis of the apparent species specificity previously observed for PSA. Expression in salivary gland is best attributed to identity between the nucleotide sequences of the PSA promoter and of a mouse glandular kallikrein normally secreted by the salivary gland.

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