Mouse Mammary Tumor Virus Env–Derived Peptide Associates with Nucleolar Targets in Lymphoma, Mammary Carcinoma, and Human Breast Cancer

Bar-Sinai, Allan; Bassa, Nir; Fischette, Maria R.; Gottesman, Michael M.; Love, Dona C.; Hanover, John A.; Hochman, Jacob

doi:10.1158/0008-5472.can-04-3879

Cited by 21 publications

(35 citation statements)

References 29 publications

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“…The resulting plasmid was confirmed by sequencing and the expressed His-tagged p14 protein was purified on a TALON (Clontech) affinity column and purity confirmed as previously shown (18).…”

Section: N-terminal His-tagged P14mentioning

confidence: 99%

“…p14 (and p21) was visualized using the polyclonal anti-p14 antibody (18), horseradish peroxidase-linked donkey anti- …”

Section: Western Blotsmentioning

confidence: 99%

“…Its mass was subsequently determined by mass spectrometry to be 11 kDa (17). The nucleolar localization of p14 is not limited to murine lymphomas, as it also occurs in mouse mammary carcinoma cell lines that harbor MMTV (18). Cell lines devoid of MMTV (either lymphoma or mammary carcinoma) do not show any cross-reaction with anti-p14 antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…Cell lines devoid of MMTV (either lymphoma or mammary carcinoma) do not show any cross-reaction with anti-p14 antibodies. Furthermore, using antibodies generated against recombinant p14, this protein was identified in nucleoli of a subset of human breast cancers (18). Comparing the sequence of p14 with the parallel sequence of a provirus isolated from human breast cancer revealed 86% homology between the two (18).…”

Section: Introductionmentioning

confidence: 99%

“…This was also the first time that any MMTV protein was observed in this compartment. Following these studies, 9 p14-binding proteins have been identified (18). Four of these B23 (nucleophosmin), L5, La, and acidic ribosomal binding protein are nucleolar proteins involved in a variety of cellular processes.…”

Section: Introductionmentioning

confidence: 99%

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The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator.

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Section: N-terminal His-tagged P14mentioning

confidence: 99%

“…p14 (and p21) was visualized using the polyclonal anti-p14 antibody (18), horseradish peroxidase-linked donkey anti- …”

Section: Western Blotsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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Do Viruses Cause Breast Cancer?

Lawson

2009

Methods in Molecular Biology

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Because mouse mammary tumor virus (MMTV; the Bittner virus) is the proven cause of breast cancer in both field and experimental mice, similar viruses have long been suspects as a potential cause of human breast cancer. MMTV-like viral genetic material has been identified in human breast tumors, but there is no definitive evidence whether MMTV is causal and not merely an innocuous infection in humans. High-risk human papilloma viruses (HPVs), Epstein-Barr (EBV), and other viruses also have been identified in human breast tumors, but again there is no definitive evidence for a causal role. Any viral hypothesis as a cause of breast cancer must take into account the most striking epidemiologic feature of human breast cancer, the three- to sixfold differences in mortality and up to eightfold differences in incidence between some Asian and Western populations. These differences dramatically lessen to a two- to threefold difference within one or two generations of migration of females from low to high risk of breast cancer countries. In this chapter, a plausible explanation for these phenomena is offered; that is, the hypothesis that oncogenic viruses such as MMTV and high-risk HPVs may initiate some breast cancers in most populations. Furthermore, dietary patterns are suggested to determine circulating sex hormone levels, which in turn promote the replication of the hormone-dependent viruses MMTV and HPV. In addition, diet and hormones promote growth of both normal and malignant cells. Finally, the hypothesis that migrants from low to high risk of breast cancer countries change their food consumption patterns is suggested, which leads to higher circulating hormone levels, which in turn promotes viral replication, which initiates breast oncogenesis, which is enhanced by sex and growth hormones.

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