Mouse mammary tumor-like virus and human breast cancer

Abstract

Park et al. from Melbourne, Australia, report their failure toidentify by standard polymerase chain reaction (PCR)techniques, mouse mammary tumor virus (MMTV)-likeenv sequences in DNA extracted from 42 formalin-fixedinvasive breast cancer specimens, all from women living inMelbourne [1]. This negative outcome is in stark contrastto the many reports of the positive identification ofMMTV-like env sequences in breast cancers from inde-pendent laboratories in Australia, Argentina, China, Italy,Mexico, Tunisia, and the United States [2]. However, inpast years other workers have also failed to identify thesesequences in breast cancers [3–5].One reason for these differing outcomes is likely to bethe use of different primers for PCR analyses. Park et al.used primers that differ entirely from those identified ini-tially by the Pogo group from New York [6]. These latterprimers have been used in virtually all the more recentpositive identifications of MMTV-like env sequences inbreast tumors. Further, the identification and nuclearlocation of these sequences have been confirmed by in situPCR techniques which largely overcome the problem ofcontamination often associated with standard PCR [2, 7].In addition there is a concern about the ability of theprimers used by Park et al. to detect MMTV envelopesequences, since they used ‘‘fresh dilutions of p203[MMTV carrying plasmid] to yield five plasmid copiesagainst 10 ng MMTV – negative human genomic DNA’’ asa control. Clearly this plasmid has 100% complementarysequences to the primers chosen. Even though, they showin Fig. 1 the primers they used have perfect homology to anumber of MMTV’s from mice, they do not show thatthese primers are able to amplify sequences from mousegenomic DNA carrying these MMTV’s (ideally mixed withMMTV negative human genomic DNA) or more impor-tantly, carrying different (wild) isolates of MMTV that mayhave different sequences in these primer complementaryregions.The interesting question that arises from these variationsin findings is ‘‘why is it so?’’, why do primers identified byPogo give positive outcomes, but other primers also basedon MMTV envelope gene sequences give negative out-comes? The brief answer is, ‘‘we do not know’’.In our view, the evidence for a possible role of MMTV-like virus in human breast cancer is substantial. We haveoutlined this evidence in recent publications [2, 8].