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De-regulation of endogenous retrotransposons in mouse mammary carcinomas of diverse etiologies
B B Asch1, H L Asch, D L Stoler
1Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Abstract:
Of the several families of endogenous retrovirus-like elements present in the mouse genome, only mouse mammary tumor virus has been analyzed for its role in mammary carcinogenesis. Very little is known about the expression and activities of other retro-elements in normal and malignant mammary epithelium. We have begun investigating the possible involvement of the 3 retrotransposons, intracisternal A particles (IAPs), murine-leukemia-virus-related (MuLVr) elements, and VL30 sequences, in neoplastic progression of the mammary gland in BALB/c mice. The purpose of the present study was to determine which of these elements was active in primary mammary carcinomas induced by chemical, hormonal and viral agents. Each of these cancers had aberrant expression of at least one of the latter retrovirus-like components. IAP and/or MuLVr sequences were over-expressed 3 to 100-fold in most of the tumors as compared with normal mammary tissue, whereas VL30 expression was markedly decreased by 5- to 35-fold in almost all of the neoplasms. Our results thus demonstrate that substantial changes in the expression of one or more of these 3 families of endogenous retrotransposons are triggered during mouse mammary tumorigenesis, regardless of etiology. Direct involvement of IAPs and MuLVr elements in neoplastic progression by transposition and insertional mutagenesis in the genome of several hematopoietic cell types has already been demonstrated. Their elevated expression in many mammary carcinomas suggests that these retrotransposons may also be potential participants in some pathways of mouse mammary carcinogenesis.
Insights
Endogenous retrotransposons, including intracisternal A particles (IAPs) and murine-leukemia-virus-related (MuLVr) elements, show altered expression in mouse mammary tumors. This suggests their potential role in mammary carcinogenesis, regardless of the tumor
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Mouse mammary tumor virus is the only endogenous retrovirus-like element studied for mammary carcinogenesis.
- Expression and activity of other retro-elements in normal and malignant mammary epithelium are largely unknown.
- Investigating three retrotransposon families: IAPs, MuLVr, and VL30 sequences in BALB/c mice.
Purpose of the Study:
- Determine the activity of IAPs, MuLVr, and VL30 in primary mammary carcinomas.
- Analyze retrotransposon activity induced by chemical, hormonal, and viral agents.
- Assess the role of these retroelements in mammary gland neoplastic progression.
Main Methods:
- Analysis of retrotransposon expression in primary mammary tumors and normal mammary tissue.
- Quantification of IAP, MuLVr, and VL30 sequence expression levels.
- Comparison of retrotransposon expression across tumors induced by different etiological agents.
Main Results:
- Aberrant expression of at least one retrovirus-like component was observed in all tested mammary carcinomas.
- IAP and/or MuLVr sequences were over-expressed 3- to 100-fold in most tumors compared to normal tissue.
- VL30 expression was decreased 5- to 35-fold in almost all mammary neoplasms.
Conclusions:
- Substantial changes in the expression of IAPs, MuLVr, or VL30 are triggered during mouse mammary tumorigenesis, irrespective of the cause.
- Elevated expression of IAPs and MuLVr in mammary carcinomas suggests their potential involvement in mammary carcinogenesis.
- Further research is warranted to elucidate the specific mechanisms by which these retrotransposons contribute to tumor development.