Decoding the mystery of MMTV-like virus and its relationship with breast cancer metastasis.

BACKGROUND: MMTV causes mammary tumors in mice, and it is associated with invasive and aggressive forms of breast cancer in humans. However, the underlying mechanisms are yet unknown. We aimed to determine the MMTV-like virus (MMTV-LV) association with histological types of breast cancer, nodal involvement, and metastasis. METHODS: First, 105 breast cancer biopsies and 15 disease-free biopsies were collected. Details of clinicopathological characteristics were retrieved from patients' records. The status of MMTV-LV was already known for these biopsy samples. Associations of MMTV-LV prevalence with LNM status and metastatic history were determined. Next, quantitative PCR (qPCR) was used to quantify env gene mRNA in biopsies positive for MMTV-LV. Expression of the env gene was compared against different histopathological types of mammary tumor, LNM status, and metastasis by performing Ordinary One Way ANOVA followed by Tukey's multiple comparisons test. RESULTS: MMTV-LV prevalence was found to have no significant association with LNM or metastatic history. As compared to normal control, expression of the env gene was significantly higher (>2.8 folds) in invasive samples (P-value: < 0.01). Expression was also higher (3.28 and 2.89 folds) in patient samples with LNM (P-value: 0.0006) or metastatic history (P-value: < 0.0001), respectively. CONCLUSION: We conclude that MMTV-LV prevalence is not associated with LNM status or breast cancer metastasis; samples with invasive phenotypes, nodal involvement, and metastasis exhibit significantly higher expression of the MMTV-like env gene.

MMTV-LIKE virus and c-myc over-expression are associated with invasive breast cancer.

Development and progression of breast cancer is an outcome of strong interplay between proto-oncogenes as well as environmental factors. Among proto-oncogenes, c-myc, a multifunctional transcription factor (TF), is one of the most highlighted one, whereas among environmental factors Mouse Mammary Tumor Virus (MMTV)-like virus is a widely discussed agent. Both, c-myc and MMTV-like virus, are known to individually correlate with the poor prognosis of breast cancer. However, no study has ever been reported to determine their mutual association in breast cancer patients. In this study, our aim was to quantify and compare c-myc mRNA in MMTV-like virus-positive and virus-negative-histopathological types of breast cancer. At first, biopsy samples of 105 breast cancer patients with known histopathological types were collected and screened for the presence of MMTV-like virus. To quantify mRNA level of c-myc, quantitative-Polymerase Chain Reaction (qPCR) was used. Next, c-myc expression was compared in MMTV-like virus-positive and virus-negative-histopathological types as of breast cancer. Statistical analysis was done using GraphPad Prism 7 Software. Molecular analysis revealed that 69 (65.72%) out of 105 samples were positive for MMTV-like virus. Moreover, invasive types of breast cancer exhibited increased (3-13 folds higher) expression of c-myc as compared to baseline representing normal control comprising of 15 tumor-free biopsy samples of breast cancer patients. Whereas, non-invasive types of breast cancer showed only 1-3 folds increase in the expression of c-myc as compared to normal control. Furthermore, virus-positive and virus-negative samples had different levels of c-myc mRNA. Positive status of MMTV-like virus was noticed to significantly associate with c-myc expression increasing it from 1.87-folds in virus-negative patient samples to 4.31-folds in virus-positive patient samples (p-value: <0.0001). Whereas, increase in the expression of c-myc was only 1.14-folds higher in 2 (13.33%) virus-positive-normal control samples as compared to 13 (86.67%) virus-negative-normal control samples (P-value: <0.01). In conclusion, it is suggested that presence of MMTV-like virus and over-expression of c-myc may be used as markers of invasion of breast cancer.