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Potential Mouse Tumor Model for Pre-Clinical Testing of Mage-Specific Breast Cancer Vaccines

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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.

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Authors and Affiliations

  1. Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX

    Roza K. Sypniewska, Lieve Hoflack & Claudia Gravekamp

  2. Arizona Cancer Center, Tucson, AZ, USA

    David J. Bearss

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  1. Roza K. Sypniewska
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  2. Lieve Hoflack
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  3. David J. Bearss
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  4. Claudia Gravekamp
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Sypniewska, R.K., Hoflack, L., Bearss, D.J. et al. Potential Mouse Tumor Model for Pre-Clinical Testing of Mage-Specific Breast Cancer Vaccines. Breast Cancer Res Treat 74, 221–233 (2002). https://doi.org/10.1023/A:1016367104015

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