Center for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan.
Department of Biotechnology and Genetic Engineering, Hazara University Mansehra, Khyber Pakhtunkhwa, Pakistan.
Infect Genet Evol. 2021 Jul;91:104827. doi: 10.1016/j.meegid.2021.104827. Epub 2021 Mar 29.
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.
乳腺癌的发展和进展是原癌基因与环境因素强烈相互作用的结果。在原癌基因中，多功能转录因子（TF）c-myc 是最受关注的原癌基因之一，而在环境因素中，鼠乳腺肿瘤病毒（MMTV）样病毒是一个广泛讨论的因素。c-myc 和 MMTV 样病毒都与乳腺癌的预后不良有关。然而，尚未有研究报道确定它们在乳腺癌患者中的相互关联。在这项研究中，我们的目的是定量比较 MMTV 样病毒阳性和病毒阴性的乳腺癌组织病理学类型中 c-myc mRNA 的表达。首先，收集了 105 例已知组织病理学类型的乳腺癌患者的活检样本，并对 MMTV 样病毒的存在进行了筛查。为了定量检测 c-myc mRNA 的水平，我们使用了实时聚合酶链反应（qPCR）。接下来，我们比较了 MMTV 样病毒阳性和病毒阴性的乳腺癌组织病理学类型中 c-myc 的表达。统计分析使用 GraphPad Prism 7 软件进行。分子分析显示，105 例样本中有 69 例（65.72%）为 MMTV 样病毒阳性。此外，与基线相比，侵袭性乳腺癌的 c-myc 表达增加了 3-13 倍，基线为 15 例乳腺癌患者肿瘤无复发生物活检样本组成的正常对照。而非侵袭性乳腺癌的 c-myc 表达仅增加了 1-3 倍。此外，病毒阳性和病毒阴性样本的 c-myc mRNA 水平不同。MTV 样病毒阳性状态与 c-myc 表达显著相关，使病毒阴性患者样本中的 c-myc 表达从 1.87 倍增加到病毒阳性患者样本中的 4.31 倍（p 值：<0.0001）。而在 2 例（13.33%）病毒阳性正常对照样本中，c-myc 表达仅增加了 1.14 倍，而在 13 例（86.67%）病毒阴性正常对照样本中增加了 1.14 倍（p 值：<0.01）。总之，建议将 MMTV 样病毒的存在和 c-myc 的过度表达作为乳腺癌侵袭的标志物。
