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Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter.

Etkind PR, Stewart AF, Wiernik PH - Infect. Agents Cancer (2008)

Bottom Line: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members.The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent.

View Article: PubMed Central - HTML - PubMed

Affiliation: Our Lady of Mercy Medical Center-Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA. petkind@olmhs.org

ABSTRACT

Background: The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members.

Results: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members. The amplified env gene sequences were 98.0%-99.6% homologous to the MMTV env sequences found in the GR, C3H, and BR6 mouse strains. The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.

Conclusion: The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice.

No MeSH data available.


Related in: MedlinePlus

Amplification of 250 bp of MMTV-like env gene and 630 bp of MMTV-like LTR gene by PCR. A, Ethidium bromide stained 1% agarose gel electrophoresis of amplified MMTV-like env sequences; B, Southern blot [13] hybridization of A using 5' P32 end-labeled 23-mer probe. Lanes 2, 3 and 4 represent the amplified DNA from the daughter, mother and father respectively. C, Ethidium bromide stained 1.8 % agarose gel electrophoresis of amplified MMTV-like LTR sequences; D, Southern blot [13] hybridization of C using 5' P32 end-labeled 20 mer probe. Lanes 2, 3, and 4 represent amplified DNA from mother, daughter and father respectively. In Panels A-D, Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. M is the molecular weight marker ΦX174 RF DNA cut with the restriction enzyme HaeIII.
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Figure 2: Amplification of 250 bp of MMTV-like env gene and 630 bp of MMTV-like LTR gene by PCR. A, Ethidium bromide stained 1% agarose gel electrophoresis of amplified MMTV-like env sequences; B, Southern blot [13] hybridization of A using 5' P32 end-labeled 23-mer probe. Lanes 2, 3 and 4 represent the amplified DNA from the daughter, mother and father respectively. C, Ethidium bromide stained 1.8 % agarose gel electrophoresis of amplified MMTV-like LTR sequences; D, Southern blot [13] hybridization of C using 5' P32 end-labeled 20 mer probe. Lanes 2, 3, and 4 represent amplified DNA from mother, daughter and father respectively. In Panels A-D, Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. M is the molecular weight marker ΦX174 RF DNA cut with the restriction enzyme HaeIII.

Mentions: DNA from malignant tissue of each family member was amplified using single round PCR with primers specific for a 250 basepair (bp) region of the MMTV env gene and not found in any human endogenous retroviral sequences i.e HERV-Ks [1,4,11,12]. Figure 2A represents the ethidium bromide-stained agarose gel electrophoresis of an MMTV env primed PCR from each of the three family members and 2B is the hybridized Southern blot [13]. Lanes 2, 3, and 4 in both Figure 2A and 2B represent the amplified DNA from the daughter, mother, and father respectively. Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. Positive hybridization results with the radiolabled internal 23-mer oligonucleotide probe that contained MMTV-env gene sequences indicated that this MMTV-specific sequence was present in the amplified 250-bp fragment and that the bands in the agarose gel were MMTV specific.


Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter.

Etkind PR, Stewart AF, Wiernik PH - Infect. Agents Cancer (2008)

Amplification of 250 bp of MMTV-like env gene and 630 bp of MMTV-like LTR gene by PCR. A, Ethidium bromide stained 1% agarose gel electrophoresis of amplified MMTV-like env sequences; B, Southern blot [13] hybridization of A using 5' P32 end-labeled 23-mer probe. Lanes 2, 3 and 4 represent the amplified DNA from the daughter, mother and father respectively. C, Ethidium bromide stained 1.8 % agarose gel electrophoresis of amplified MMTV-like LTR sequences; D, Southern blot [13] hybridization of C using 5' P32 end-labeled 20 mer probe. Lanes 2, 3, and 4 represent amplified DNA from mother, daughter and father respectively. In Panels A-D, Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. M is the molecular weight marker ΦX174 RF DNA cut with the restriction enzyme HaeIII.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2277433&req=5

Figure 2: Amplification of 250 bp of MMTV-like env gene and 630 bp of MMTV-like LTR gene by PCR. A, Ethidium bromide stained 1% agarose gel electrophoresis of amplified MMTV-like env sequences; B, Southern blot [13] hybridization of A using 5' P32 end-labeled 23-mer probe. Lanes 2, 3 and 4 represent the amplified DNA from the daughter, mother and father respectively. C, Ethidium bromide stained 1.8 % agarose gel electrophoresis of amplified MMTV-like LTR sequences; D, Southern blot [13] hybridization of C using 5' P32 end-labeled 20 mer probe. Lanes 2, 3, and 4 represent amplified DNA from mother, daughter and father respectively. In Panels A-D, Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. M is the molecular weight marker ΦX174 RF DNA cut with the restriction enzyme HaeIII.
Mentions: DNA from malignant tissue of each family member was amplified using single round PCR with primers specific for a 250 basepair (bp) region of the MMTV env gene and not found in any human endogenous retroviral sequences i.e HERV-Ks [1,4,11,12]. Figure 2A represents the ethidium bromide-stained agarose gel electrophoresis of an MMTV env primed PCR from each of the three family members and 2B is the hybridized Southern blot [13]. Lanes 2, 3, and 4 in both Figure 2A and 2B represent the amplified DNA from the daughter, mother, and father respectively. Lane 1 containing no template DNA and lanes 5, 6, and 7 containing normal breast tissue DNA from three separate individuals represent negative controls for sample contamination. Positive hybridization results with the radiolabled internal 23-mer oligonucleotide probe that contained MMTV-env gene sequences indicated that this MMTV-specific sequence was present in the amplified 250-bp fragment and that the bands in the agarose gel were MMTV specific.

Bottom Line: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members.The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent.

View Article: PubMed Central - HTML - PubMed

Affiliation: Our Lady of Mercy Medical Center-Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA. petkind@olmhs.org

ABSTRACT

Background: The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members.

Results: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members. The amplified env gene sequences were 98.0%-99.6% homologous to the MMTV env sequences found in the GR, C3H, and BR6 mouse strains. The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.

Conclusion: The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice.

No MeSH data available.


Related in: MedlinePlus