Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

Abstract

Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings. Cancer Res; 70(9); 3576-85. ©2010 AACR.

Presence of Human Papillomavirus and Epstein-Barr Virus in Breast Cancer Biopsies as Potential Risk Factors

“…In this study, the presence of HPV was detected in 63.6% of breast cancer samples, while only 4.5% of benign pathology tissue biopsies were positive for this virus. This detection frequency is within the previously published worldwide range, with a prevalence ranging from 10-86% 4,5,14,16,[29][30][31][32] , where the works by Akil, et al 4 in 2008 and Antonsson, et al 30 in 2011 detected 61.06 and 50% of HPV DNA-positive cases by means of multiplex PCR and assembly PCR, respectively.…”

“…Currently, there are well known risk factors associated with breast cancer; however, in most women, identifying a particular factor related to the development of the disease is not possible 3 . In the past few decades, the action of a group of tumor-producing viruses has been considered to be an important factor in the development of cancer in both experimental and human models 4,5 . The human papillomavirus (HPV) is the etiologic agent of cervical cancer, and the Epstein-Barr virus (EBV) is mainly associated with nasopharyngeal carcinoma and Burkitts lymphoma.…”

Lack of Association of Mouse Mammary Tumor Virus-Like Sequences in Iranian Breast Cancer Patients

“…These data were then highlighted in a study of the prevalence of MMTV DNA PCR positivity in breast cancer patients from Vietnam with 1% positivity and Australia with 42% positivity [22]. MMTV-like env sequences have also been detected in human breast samples from women in Australia, Argentina, China, Tunisia and United States [23]. …”

Tumorigenesis related to retroviral infections

“…Companion animals might contribute to the transmission of MMTV between mouse and man [51]. MMTV-like virus DNA has been detected in several human cancers including breast, liver, ovarian, prostate, endometrial, and skin malignancies [52,53]. There is increased speculation that a human relative of MMTV (HMTV) might be involved in human carcinogenesis; however, this is not yet confirmed [12].…”