Potential mouse tumor model for pre-clinical testing of Mage-specific breast cancer vaccines

Roza K. Sypniewska, Lieve Hoflack, David J. Bearss, Claudia Gravekamp

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Currently, there is a lack of suitable pre-clinical mouse models for testing and optimization of experimental cancer vaccines. Here, in situ developed mammary tumors of MMTV-v-Ha-ras and MMTV-c-myc transgenic mice and normal mammary, liver, spleen, and testis were screened for expression of tumor-associated antigens (TAA) Mage-b1/2/3 by reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blot hybridization. Mage-b1/2/3 are homologues of the human TAA MAGE-B1/2/3. Expression of these human MAGE genes has been found in tumors of various histological types, including breast cancer [39]. Mage-specific RT-PCR products (using primers that amplify all three Mage-b1/2/3) were detected in mammary tumors of the MMTV-v-Ha-ras and MMTV-c-myc transgenic mice and in testis, but not in other normal tissues. RT-PCR products obtained from the mammary tumors (using primers that amplify the complete protein-encoding region of Mage-b1/2/3) were cloned and sequenced, and appeared to be most homologous with Mage-b3. Comparison of the Mage-b3 gene in mammary tumors and normal tissues suggest that somatic mutations did not occur in the Mage-b3 gene of the ras- and myc-induced mammary tumors. In addition, no differences were found between the Mage-b3 cDNA of testis, the only normal tissue that expresses Mage-b3, and Mage-b3 in genomic DNA of normal kidney, where Mage-b3 is silent. The MMTV-v-Ha-ras and MMTV-c-myc transgenic mice of this study are the first immune competent mouse models with in situ developed mammary tumors in which the expression of Mage-b3 TAA has been demonstrated. This makes them potentially suitable as a mouse model for pre-clinical testing of Mage-specific cancer vaccines in vivo.

Original languageEnglish (US)
Pages (from-to)221-233
Number of pages13
JournalBreast Cancer Research and Treatment
Volume74
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Cancer Vaccines
Breast Neoplasms
Neoplasm Antigens
Reverse Transcriptase Polymerase Chain Reaction
Neoplasms
Transgenic Mice
Testis
myc Genes
ras Genes
Southern Blotting
Genes
Breast
Spleen
Complementary DNA
Kidney
Mutation
Liver
DNA

Keywords

  • Cancer vaccines
  • CTL epitopes
  • Mage-b3
  • Mouse mammary tumor models
  • Pre-clinical testing of cancer vaccines
  • Transgenic mice

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Potential mouse tumor model for pre-clinical testing of Mage-specific breast cancer vaccines. / Sypniewska, Roza K.; Hoflack, Lieve; Bearss, David J.; Gravekamp, Claudia.

In: Breast Cancer Research and Treatment, Vol. 74, No. 3, 2002, p. 221-233.

Research output: Contribution to journalArticle

Sypniewska, Roza K. ; Hoflack, Lieve ; Bearss, David J. ; Gravekamp, Claudia. / Potential mouse tumor model for pre-clinical testing of Mage-specific breast cancer vaccines. In: Breast Cancer Research and Treatment. 2002 ; Vol. 74, No. 3. pp. 221-233.
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