Human Mammary Tumor Virus (HMTV) in Endometrial Carcinoma

Deligdisch, Liane; Marin, Tania; Lee, Anna T.; Etkind, Polly R.; Holland, James F.; Melana, Stella M.; Pogo, Beatríz G. T.

doi:10.1097/igc.0b013e3182980fc5

Cited by 19 publications

(23 citation statements)

References 18 publications

(25 reference statements)

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“…PCR products were tested for the presence of murine mitochondrial (MoMt) and genomic DNA to exclude contamination. The methods used were as described by Deligdisch et al [27] and outlined below: Detection of mouse mitochondrial DNA sequences. …”

Section: Methodsmentioning

confidence: 99%

Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer

Nartey

Mazzanti

Melana

et al. 2017

Infect Agents Cancer

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BackgroundThere is substantial evidence that a virus homologous to mouse mammary tumor virus (MMTV) may have a role in human breast cancer. The present study indicates that those who developed breast cancer associated with an MMTV-like virus had this virus in their non-cancerous breast tissues years before the cancer developed.MethodsPolymerase chain reaction (PCR) techniques and sequencing were used to identify MMTV-like envelope gene sequences (MMTV-like env sequences) in Australian benign breast biopsy specimens from women who several years later developed breast cancer. Murine contamination was excluded by stringent laboratory procedures, and the absence of intracisternal A particle sequences and mitochondrial cyclooxygenase sequences.ResultsMMTV-like env sequences (also called HMTV sequences to denote their source) were found in 9 of 25 breast cancer specimens (36%). Among 25 non-cancerous breast biopsies of these same patients taken 1 to 11 years earlier, six contained MMTV-like sequences (24%). Five of the six were among the nine virally-associated breast cancers. In two pairs of specimens, benign and malignant, env sequences were 97% identical.ConclusionsThe identification of MMTV (MMTV-like) sequences in breast tissues prior to the development of MMTV positive breast cancer fulfills a key criterion for a possible causal role for the MMTV-like virus in human breast cancer.

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Section: Methodsmentioning

confidence: 99%

Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer

Nartey

Mazzanti

Melana

et al. 2017

Infect Agents Cancer

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“…The product is 251 bp. Both HMTV- env PCR reactions were performed in a thermocycler under the following conditions [32] with minimal modifications: a cycle of 95°C for 5 min, followed by 35 cycles of 95°C for 30 sec, 58°C for 30 sec, 72°C for 30 sec, and a final step of 72°C for 7 min. Each sample was tested three times to assure the reproducibility of the reaction.…”

Section: Methodsmentioning

confidence: 99%

“…One of these assays is for the detection of cytochrome oxidase, a gene that is part of MoMt [32]. To test for MoMt, the following primers were used: mt15982F (5′- AGACGCACCTACGGTGAAGA-3′) and mt16267R (5′-AGAGTTTTGGTTCACGGAACATGA-3′) [32].…”

Section: Methodsmentioning

confidence: 99%

“…To test for MoMt, the following primers were used: mt15982F (5′- AGACGCACCTACGGTGAAGA-3′) and mt16267R (5′-AGAGTTTTGGTTCACGGAACATGA-3′) [32]. The product yields an amplicon of 286 bp.…”

Section: Methodsmentioning

confidence: 99%

“…The product yields an amplicon of 286 bp. A semi-nested PCR was then performed using the primers mt16115F (5′-TGCCAAACCCCAAAAACACT-3′) and mt16267R, which results in a 153 bp amplicon [32]. The PCR product was transferred from the gel to a positively charged nylon membrane and hybridized with a 32 P-labeled oligonucleotide MoMt DNA probe (5′-GAACTAGAATTGATCAGGCAT-3′).…”

Section: Methodsmentioning

confidence: 99%

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Human Mammary Tumor Virus (HMTV) sequences in human milk

Nartey

Moran

Marin

et al. 2014

Infect Agents Cancer

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BackgroundRetroviral sequences 90-95% homologous to the mouse mammary tumor virus (MMTV) were present in 38% of the breast cancers studied from American women and were not detectable in non-tumor breast tissue from the same patient. The entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. This virus was designated as human mammary tumor virus (HMTV). Hormone response elements present in the HMTV Long-Terminal-Repeat (LTR) suggest a mechanism for association of HMTV with hormonally responding tissues. In fact, the incidence of HMTV sequences is higher in gestational breast cancers, which are associated with hormonal changes. Milk epithelial cells are also under hormonal regulation and therefore are excellent specimens for HMTV sequence detection.MethodsThe HMTV sequence was studied in milk samples from lactating women recruited with increased risk of breast cancer because they had undergone breast biopsies (Biopsy-Group) and lactating women without breast biopsies (Reference-Group).ResultsHMTV-env sequences were detected by PCR in milk of 7.61% of 92 women of the Reference-Group and in 20.55% of 73 women of the Biopsy-Group (p: 0.015). The sequences were 94-98% homologous to MMTV. HMTV-env and HMTV-env/LTR junction sequences were detected in high-speed pellet RNA, implying the presence of HMTV viral particles. PCR assays to detect the murine mitochondrial cytochrome oxidase gene and intracisternal-A-type particle sequences were performed to rule out mouse mitochondrial or genomic DNA contamination. Eight women of the 73 Biopsy-Group participants had breast cancer and the milk of only one of these eight women had HMTV-env sequences. In the remaining 65 women of the Biopsy-Group, under enough clinical suspicion to lead to biopsy, HMTV was detected in 14, nearly three times the number of milks as compared to the Reference-Group (21.54% versus 7.61%; p: 0.016).ConclusionThe significance of HMTV in milk from the Reference-Group, the greater frequency in the milk of women who had undergone a breast biopsy and its possible infectivity for infants are important questions under study. The similarity of HMTV to MMTV is striking and suggests one possible avenue for viral transmission in humans.

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