Mouse mammary tumor virus-like sequences in human breast cancer.
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.
Lawson
James S
JS
Faculty of Science and School of Medical Sciences, School of Biotechnology and Biomolecular Sciences, University of New South Wales, UNSW Sydney, Australia. james.lawson@unsw.edu.au
Glenn
Wendy K
WK
Salmons
Brian
B
Ye
Yulan
Y
Heng
Benjamin
B
Moody
Patrick
P
Johal
Harpreet
H
Rawlinson
William D
WD
Delprado
Warick
W
Lutze-Mann
Louise
L
Whitaker
Noel J
NJ
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015752:Genes, env; D006801:Humans; D007150:Immunohistochemistry; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D051155:Wnt1 Protein / Q000096:biosynthesis / Q000235:genetics
D000957:Antigens, Viral, Tumor; D051155:Wnt1 Protein; C040612:glycoprotein 52 antigen, Mouse mammary tumor virus