Detection of the env MMTV-homologous sequences in mammary carcinoma patient intestine lymphoid tissue

Лушникова, А. А.; Kryukova, I. N.; Ротин, Д Л; Lubchenko, L. N.

doi:10.1007/s10630-005-0001-5

Cited by 12 publications

(8 citation statements)

References 8 publications

(12 reference statements)

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“…Several groups have confirmed and extended our observations 22‐32. There were, however, a few groups that were unable to reproduce our findings, because they either did not use the same technology,33‐36 used a low number of samples,33, 36 did not evaluate the quality of the DNA used,34 or did not indicate the origin of samples 33, 36.…”

Section: Mmtv‐like Env Gene Sequences In Human Breast Cancersupporting

confidence: 60%

Human mammary tumor virus in inflammatory breast cancer

Pogo

Holland

Levine

2010

Cancer

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The authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of American women. These sequences were not found in normal breasts or other tumors. A whole proviral structure was detected in 2 tumors. Breast cancer cells in culture were shown to contain and shed betaretroviral particles. This virus was designated human mammary tumor virus (HMTV). The authors have investigated the presence of HMTV sequences in a variety of breast conditions and geographic locations. Here they report that inflammatory breast cancer from American women shows a higher incidence of viral sequences (71%) than sporadic breast cancers. Similar incidence has been found in inflammatory breast cancers from Tunisia, and in gestational breast cancers. Because these conditions represent highly invasive malignancies, it is concluded that HMTV is sometimes associated with a particularly malignant phenotype. Cancer 2010;116(11 suppl):2741-4. V C 2010 American Cancer Society.KEYWORDS: inflammatory breast cancer, human mammary tumor virus, mouse mammary tumor virus, viral oncogenesis, breast cancer.Since Bittner 1 described the mouse mammary tumor virus (MMTV) as the agent involved in mouse mammary carcinogenesis in 1936, MMTV has been regarded as a potential model for human disease.In the 1970s and 1980s, several reports claimed that MMTV-like sequences were present in breast cancer samples but absent in normal tissues (reviewed in Pogo and Holland 2 ), that immunoreactivity was found in breast cancer tissue against the envelope protein (Env) of MMTV that was absent in normal tissue, [3][4][5][6][7] and that antibodies against Env were found in patients with breast cancer. 8 Furthermore, viral particles with morphological characteristics of a retrovirus were detected in 60% of milk from patients with a history of breast cancer but only in 5% of milk from normal individuals. 9 However, the possibility of an exogenous infection by a virus similar to MMTV was challenged by the finding of Westley and May 10 that the human genome contains retroviral sequences that are 50% homologous to MMTV. There were also reports questioning the specificity of the antigen used in immunological studies. 11 Furthermore, contrary to previous findings, retroviral particles were found in a pool of 300 normal human milk samples from which viral particles were purified and their proteins characterized. 12 In the early 1990s, we started to investigate this problem using a drastically different approach. We applied the then new PCR technology using primers for the MMTV env gene, whose sequences were not present in the human genome, and analyzed only breast cancer samples obtained directly from the operating room to avoid contamination. Most previous research was done with established cell lines whose origins and history were dubious. The competence of these established cell lines to represent the original tissue has recently been challenged by us. 13,14 Our first publication on the...

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Section: Mmtv‐like Env Gene Sequences In Human Breast Cancersupporting

confidence: 60%

Human mammary tumor virus in inflammatory breast cancer

Pogo

Holland

Levine

2010

Cancer

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“…In humans, MMTV infects lymphocytes located in the intestine and randomly infects and integrates into the human genome located in normal breast epithelial cells ( 67 – 70 , 107 ).…”

Section: Mouse Mammary Tumor Virusmentioning

confidence: 99%

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Salmons²,

2018

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BackgroundAlthough the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein–Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence.The evidenceMMTV and human breast cancer—the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer—the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer—the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer—the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal.ConclusionThe influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

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“…There are close parallels between MMTV-associated cancer biology in both human breast cancer and mouse mammary tumors. (i) MMTV has been identified globally in human breast cancer and mouse mammary tumors ( 2 , 8 ), (ii) MMTV virus particles have been identified in human breast cancers and mouse mammary tumors ( 9 , 10 ), (iii) MMTV has been identified in both mouse and human milk ( 1 , 11 , 12 ), (iv) nucleotide sequences and structure of the 9,900-bp long MMTV genome is 84–98% homologous in both mouse and human breast cancer ( 3 , 13 – 16 ), (v) abnormal cancer related gene expression is similar ( 17 , 18 ), (vi) MMTV-associated protein expression is similar ( 19 – 21 ), (vii) MMTV superantigen expression required for activating lymphocytes appears to be the same ( 22 – 24 ), (viii) MMTV infects intestinal B lymphocytes and randomly integrates into both the mouse and human genome ( 1 , 25 – 27 ), (ix) hormone responsiveness appears to be similar ( 28 – 30 ), (x) MMTV-associated breast cancer histology may be similar ( 5 , 6 , 31 ), (xi) there is a positive serological response to MMTV in both mouse and humans although this has not been confirmed by modern methods in humans ( 32 – 36 ), and (xii) MMTV is present in normal human breast and mouse mammary tissues prior to the development of MMTV positive breast cancer and mouse mammary tumors ( 37 – 39 ).…”

Section: Comparisons Between Mmtv-associated Mouse Mammary Tumors Andmentioning

confidence: 99%

Association of Mouse Mammary Tumor Virus With Human Breast Cancer: Histology, Immunohistochemistry and Polymerase Chain Reaction Analyses

et al. 2018

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PurposeThe purpose of this study is to determine whether mouse mammary tumor virus (MMTV)-associated human breast cancer has the same or similar histology to MMTV-associated mouse mammary tumors. Such associations may indicate a role for MMTV in human breast cancer.MethodsImmunohistochemical techniques (using antibodies directed against the signal peptide p14 of the envelope precursor protein of MMTV) and polymerase chain reaction (PCR) analyses were used to identify MMTV proteins and MMTV-like envelope gene sequences in a series of breast cancers from Australian women. The histological characteristics of these human breast cancer specimens were compared with MMTV positive mouse mammary tumors. The same methods were used to study benign breast tissues which 1–11 years later developed into breast cancer.ResultsMMTV p14 proteins were identified in 27 (54%) of 50 human breast cancers. MMTV env gene sequences were identified by PCR in 12 (27%) of 45 human breast cancers. There was a significant correlation between the presence of MMTV (identified by p14 immunohistochemistry) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.001). There was a non-significant correlation between the presence of MMTV env gene sequences (identified by PCR) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.290). MMTV p14 proteins were identified in 7 (54%) of 13 benign breast specimens that later developed into human breast cancers. MMTV by PCR was identified in two benign specimens one of whom later developed MMTV positive breast cancer.DiscussionThese observations offer evidence that MMTV may be associated with characteristic human breast cancer histology. p14-based immunohistochemistry appears to be a more reliable technique than PCR for the identification of MMTV in human breast cancer. Identification of MMTV-associated p14 proteins in benign breast tissues confirms prior PCR-based studies that MMTV infection occurs before the development of MMTV positive breast cancer.ConclusionMany MMTV positive human breast cancers have similar histology to MMTV positive mouse mammary tumors. MMTV infection identified in benign breast tissues precedes development of MMTV positive human breast cancer. When considered in the context of prior studies, these observations indicate a likely role for MMTV in human breast cancer.

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Detection of the env MMTV-homologous sequences in mammary carcinoma patient intestine lymphoid tissue

Cited by 12 publications

References 8 publications

Human mammary tumor virus in inflammatory breast cancer

Human mammary tumor virus in inflammatory breast cancer

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)

Association of Mouse Mammary Tumor Virus With Human Breast Cancer: Histology, Immunohistochemistry and Polymerase Chain Reaction Analyses

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