Endogenous Mouse Mammary Tumor Viruses (Mtv): New Roles for an Old Virus in Cancer, Infection, and Immunity

Holt, Michael; Shevach, Ethan M.; Punkosdy, George A.

doi:10.3389/fonc.2013.00287

Cited by 27 publications

(25 citation statements)

References 88 publications

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“…Although rodents are intrinsically more susceptible than humans to carcinogenesis, in wild-type rodents, sporadic cancers are relatively rare ( 1 ). In the past, mouse breeds prone to mammary tumors were produced by vertical transmission through milk or Bittner factor, which was later demonstrated to be due to MMTV ( 63 , 64 ). By contrast, viruses are not convincingly involved in HBC oncogenesis, except as probable cofactors ( 64 ).…”

Section: Animal Models Of Hbcmentioning

confidence: 99%

Canine mammary tumors as a model for human disease (Review)

2018

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Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has been focused on the dog as a model for human cancer. Dogs develop mammary tumors and other cancer types spontaneously with an intact immune system, which exhibit a number of clinical and molecular similarities to HBC. In addition to the spontaneous tumor presentation, the clinical similarities between human and canine mammary tumors (CMT) include the age at onset, hormonal etiology and course of the diseases. Furthermore, factors that affect the disease outcome, including tumor size, stage and lymph node invasion, are similar in HBC and CMT. Similarly, the molecular characteristics of steroid receptor, epidermal growth factor, proliferation marker, metalloproteinase and cyclooxygenase expression, and the mutation of the p53 tumor suppressor gene in CMT, mimic HBC. Furthermore, ductal carcinomas in situ in human and canine mammary glands are particularly similar in their pathological, molecular and visual characteristics. These CMT characteristics and their similarities to HBC indicate that the dog could be an excellent model for the study of human disease. These similarities are discussed in detail in the present review, and are compared with the in vitro and other in vivo animal models available.

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Section: Animal Models Of Hbcmentioning

confidence: 99%

Canine mammary tumors as a model for human disease (Review)

2018

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“…The Mouse Mammary Tumor Virus is a beta‐retrovirus that exists in both exogenous (MMTV) and endogenous ( Mtv ) forms (reviewed in ). MMTV is the etiological agent of mammary cancer in mice and might also be involved in breast cancers in humans .…”

Section: Introductionmentioning

confidence: 99%

Polypyrimidine tract‐binding protein binds to the 5′ untranslated region of the mouse mammary tumor virus mRNA and stimulates cap‐independent translation initiation

et al. 2016

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The 5 0 untranslated region (UTR) of the full-length mRNA of the mouse mammary tumor virus (MMTV) harbors an internal ribosomal entry site (IRES). In this study, we show that the polypyrimidine tract-binding protein (PTB), an RNA-binding protein with four RNA recognition motifs (RRMs), binds to the MMTV 5 0 UTR stimulating its IRES activity. There are three isoforms of PTB: PTB1, PTB2, and PTB4. Results show that PTB1 and PTB4, but not PTB2, stimulate MMTV-IRES activity. PTB1 promotes MMTV-IRES-mediated initiation more strongly than PTB4. When expressed in combination, PTB1 further enhanced PTB4 stimulation of the MMTV-IRES, while PTB2 fully abrogates PTB4-induced stimulation. PTB1-induced stimulation of MMTV-IRES was not altered in the presence of PTB4 or PTB2. Mutational analysis reveals that stimulation of MMTV-IRES activity is abrogated when PTB1 is mutated either in RRM1/RRM2 or RRM3/RRM4. In contrast, a PTB4 RRM1/RRM2 mutant has reduced effect over MMTV-IRES activity, while stimulation of the MMTV-IRES activity is still observed when the PTB4 RRM3/RMM4 mutant is used. Therefore, PTB1 and PTB4 differentially stimulate the IRES activity. In contrast, PTB2 acts as a negative modulator of PTB4-induced stimulation of MMTV-IRES. We conclude that PTB1 and PTB4 act as IRES trans-acting factors of the MMTV-IRES.

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“…In many species there are numerous examples of ERVs causing disease [ 10 , 42 , 43 ]. In humans alone, HERVs have been associated with cancer [ 44 – 46 ], multiple sclerosis [ 47 – 49 ], and a whole host of other diseases (see [ 50 ] for review).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Life History on Retroviral Genome Invasions

Kanda

Coulson

2015

PLoS ONE

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Endogenous retroviruses (ERV), or the remnants of past retroviral infections that are no longer active, are found in the genomes of most vertebrates, typically constituting approximately 10% of the genome. In some vertebrates, particularly in shorter-lived species like rodents, it is not unusual to find active endogenous retroviruses. In longer-lived species, including humans where substantial effort has been invested in searching for active ERVs, it is unusual to find them; to date none have been found in humans. Presumably the chance of detecting an active ERV infection is a function of the length of an ERV epidemic. Intuitively, given that ERVs or signatures of past ERV infections are passed from parents to offspring, we might expect to detect more active ERVs in species with longer generation times, as it should take more years for an infection to run its course in longer than in shorter lived species. This means the observation of more active ERV infections in shorter compared to longer-lived species is paradoxical. We explore this paradox using a modeling approach to investigate factors that influence ERV epidemic length. Our simple epidemiological model may explain why we find evidence of active ERV infections in shorter rather than longer-lived species.

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Endogenous Mouse Mammary Tumor Viruses (Mtv): New Roles for an Old Virus in Cancer, Infection, and Immunity

Cited by 27 publications

References 88 publications

Canine mammary tumors as a model for human disease (Review)

Canine mammary tumors as a model for human disease (Review)

Polypyrimidine tract‐binding protein binds to the 5′ untranslated region of the mouse mammary tumor virus mRNA and stimulates cap‐independent translation initiation

The Effect of Life History on Retroviral Genome Invasions

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