Prevalence of Mouse Mammary Tumor Virus (MMTV)-like sequences in human breast cancer tissues and adjacent normal breast tissues in Saudi Arabia

Dossary, Reem Al; Alkharsah, Khaled R.; Kussaibi, Haitham

doi:10.1186/s12885-018-4074-6

Cited by 23 publications

(26 citation statements)

References 47 publications

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“…ereafter, betaretrovirus sequences resembling MMTV were PCRcloned from breast cancer tissues derived from various countries, and the agent was referred to as the human mammary tumor virus [7,[23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease

Zhang

Bashiri

Kneteman

et al. 2020

Journal of Oncology

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Mouse mammary tumor virus (MMTV) is a betaretrovirus that plays a causal role in the development of breast cancer and lymphoma in mice. Closely related sequences that share 91–99% nucleotide identity with MMTV have been repeatedly found in humans with neoplastic and inflammatory diseases. Evidence for infection with a betaretrovirus has been found in patients with breast cancer and primary biliary cholangitis and referred to as the human mammary tumor virus and the human betaretrovirus (HBRV), respectively. Using the gold standard technique of demonstrating retroviral infection, HBRV proviral integrations have been detected in cholangiocytes, lymph nodes, and liver of patients with primary biliary cholangitis. However, the scientific biomedical community has not embraced the hypothesis that MMTV like betaretroviruses may infect humans because reports of viral detection have been inconsistent and robust diagnostic assays are lacking. Specifically, prior serological assays using MMTV proteins have produced divergent results in human disease. Accordingly, a partial HBRV surface (Su) construct was transfected into HEK293 to create an ELISA. The secreted HBRV gp52 Su protein was then used to screen for serological responses in patients with breast cancer and liver disease. A greater proportion of breast cancer patients (n = 98) were found to have serological reactivity to HBRV Su as compared to age- and sex-matched control subjects (10.2% versus 2.0%, P=0.017, OR = 5.6 [1.25–26.3]). Similarly, the frequency of HBRV Su reactivity was higher in patients with primary biliary cholangitis (n = 156) as compared to blood donors (11.5% vs. 3.1%, P=0.0024, OR = 4.09 [1.66–10.1]). While the sensitivity of the HBRV Su ELISA was limited, the assay was highly specific for serologic detection in patients with breast cancer or primary biliary cholangitis, respectively (98.0% [93.1%–99.7%] and 97.0% [93.4%–98.6%]). Additional assays will be required to link immune response to betaretrovirus infection and either breast cancer or primary biliary cholangitis.

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Section: Introductionmentioning

confidence: 99%

Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease

Zhang

Bashiri

Kneteman

et al. 2020

Journal of Oncology

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“…Table 1 enlists all these articles with summarized information extracted from these articles including information about the studied population, technique used for the detection of MMTVlike virus, target gene, number (No) of screened samples (normal, adjacent/benign, and BC) with their respective identified population-wise positivity ratios. Out of all the 40 studies, in total, 23 studies (Glenn et al 2012;Oskouee et al 2014;Bindra et al 2007;Morales-Sanchez et al 2013;Motamedifar et al 2012;Al Dossary et al 2018;Cedro-Tanda et al 2014;Etkind et al 2000;Ford et al 2004Ford et al , 2003Hafez et al 2013;Lawson et al 2010;Levine et al 1984;Mazzanti et al 2011;Melana et al 2002Melana et al , 2001Nartey et al 2017;Naushad et al 2014;Pogo et al 2010;Reza et al 2015;Shariatpanahi et al 2017;Slaoui et al 2014;Wang et al 1995) were the case-control studies in which normal, adjacent/benign, and BC samples were screened, while others were not.…”

Section: Resultsmentioning

confidence: 99%

“…The positivity ratio of MMTV-like virus detection in BC samples was varied population-wise from 0% (Oskouee et al 2014;Bindra et al 2007;Morales-Sanchez et al 2013;Motamedifar et al 2012;Park et al 2011;Tabriz et al 2013;Witt et al 2003) to 78.9% (Axel et al 1972) in all the 40 identified studies, while the positivity ratio of MMTV-like virus detection in normal and adjacent/ benign controls was varied from 0% (Oskouee et al 2014;Motamedifar et al 2012;Al Dossary et al 2018;Etkind et al 2000;Ford et al 2003;Lawson et al 2010;Mazzanti et al 2011;Naushad et al 2014;Reza et al 2015) to 32% (Glenn et al 2012) and 0% (Bindra et al 2007;Levine et al 1984;Melana et al 2002) to 33.3% (Slaoui et al 2014), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…So far, a single case-control study (Al Dossary et al 2018) has been carried out in Saudi Arabia to find out the association between MMTV-like virus and BC. They screened a total of 101 BC, 51 normal, and 93 adjacent/ benign controls using PCR technique with primers specific for the Env region of the viral genome and documented MMTV-like virus positivity ratios was higher in the adjacent/benign controls (9.7%) as compared to the normal (0%) and BC samples (5.9%).…”

Section: Resultsmentioning

confidence: 99%

“…The MMTVlike virus positivity ratio reported in these studies was varied between 0% (Oskouee et al 2014;Bindra et al 2007;Morales-Sanchez et al 2013;Motamedifar et al 2012;Park et al 2011;Tabriz et al 2013;Witt et al 2003) and 78.9% (Axel et al 1972) in BC samples. In most of the case-control studies (Glenn et al 2012;Oskouee et al 2014;Bindra et al 2007;Morales-Sanchez et al 2013;Motamedifar et al 2012;Etkind et al 2000;Ford et al 2004Ford et al , 2003Hafez et al 2013;Lawson et al 2010;Levine et al 1984;Mazzanti et al 2011;Melana et al 2002Melana et al , 2001Nartey et al 2017;Naushad et al 2014;Pogo et al 2010;Reza et al 2015;Shariatpanahi et al 2017;Slaoui et al 2014;Wang et al 1995), the positivity ratio for MMTVlike virus detection was higher in the BC samples as compared to the controls, while in some studies (Al Dossary et al 2018;Cedro-Tanda et al 2014), MMTV-like virus positivity ratio was higher in the controls as compared to the BC samples. Possible reasons for such populationspecific inequalities in MMTV-like virus detection could be non-modifiable factors such as genetic makeup and socially controllable factors like health-seeking behavior and differential access to the health facilities.…”

Section: Discussionmentioning

confidence: 99%

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Does mouse mammary tumor-like virus cause human breast cancer? Applying Bradford Hill criteria postulates

2020

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Background The role of mouse mammary tumor-like virus (MMTV-like virus) in human breast cancer (BC) has already been widely investigated worldwide with conflicting results. Although the researchers tried to establish the link between MMTV-like virus and BC through the statistical meta-analysis of the previous studies associating MMTV-like virus with BC, they failed to establish a more reliable link due to the shortcomings of the statistical meta-analysis. In the present study, we identified population-wide studies relating MMTV-like virus with BC through the PubMed search engine. Then, we examined the available data of MMTV-like virus prevalence in BC, normal/benign samples, and applied the postulates of Bradford Hill criteria on the available evidence to investigate the association between MMTV-like virus and BC. In addition, to further enhance the reliability of our outcomes, we have also evaluated the methodologies of the previous studies to address the possibility of false-negative and false-positive results. Results After a careful evaluation of the extracted data against the postulates of Bradford Hill criteria, it was observed that none of the studies fulfill all the major postulates of Bradford Hill criteria for causation including temporality, consistency, biological gradient, experiment, coherence, specificity, and analogy. Hence, no causal relationship has been suggested between MMTV-like virus and BC patients of the any included population. Conclusion The results failed to prove the causal relationship between MMTV-like virus and BC rather suggested it as a co-participant in the pathogenesis of BC.

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Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl‐2, and caspase‐3 signaling pathways in BALB/c mice

Changizi

Moslehi

Rohani

et al. 2020

J Biochem & Molecular Tox

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Despite all the new treatments, metastatic breast cancer (BC) causes many deaths. Chlorogenic acid (CGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic death pathways has been propounded as the most effective therapeutic method in various cancers. In the current study, apoptotic agents such as p53, Bax, Bcl‐2, and caspase‐3 have been investigated. The experimental groups included saline, BC, CGA, protective (PR), and treatment (TM) groups. First, 4T1 mouse BC was established and then the effects of treatment with CGA were investigated through measurement of tumor weight and volume, metastatic nodules, liver biochemical tests, hematoxylin and eosin (H&E), immunohistochemistry (IHC) staining, and real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) in experimental groups. The findings showed that CGA reduced tumor weight and volume in the PR group (P < .05) and in the TM group (P < .001). Surprisingly, it eliminated the tumors in the TM group. Metastatic nodules in the PR and TM groups were significantly reduced as compared with the BC group (P < .001). The evaluation by H&E staining showed cell apoptosis in both the PR and TM groups. The results of real‐time RT‐PCR showed that CGA therapy increased the expression ratio of Bax/Bcl‐2 (P < .001 and P < .05, respectively) and the expression of p53 (P < .001 and P < .05, respectively) and caspase‐3 genes (P < .01) in the PR and TM groups. The IHC data regarding the Bax/Bcl‐2 ratio confirmed the other results (P < .001). The findings demonstrate that CGA plays a significant role in the induction of apoptosis and the treatment of 4T1 BC tumors in BALB/c mice.

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Prevalence of Mouse Mammary Tumor Virus (MMTV)-like sequences in human breast cancer tissues and adjacent normal breast tissues in Saudi Arabia

Cited by 23 publications

References 47 publications

Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease

Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease

Does mouse mammary tumor-like virus cause human breast cancer? Applying Bradford Hill criteria postulates

Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl‐2, and caspase‐3 signaling pathways in BALB/c mice

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