Early Pathologic Changes in Experimental and Human Breast Cancer: Facts and Comments<sup>a</sup>

Squartini, F; Bistocchi, M; Sarnelli, R; Basolo, Fulvio

doi:10.1111/j.1749-6632.1986.tb16007.x

Cited by 9 publications

(2 citation statements)

References 22 publications

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“…In their study BALB/c mice which have a low or no incidence of spontaneous mammary tumors (Squartini, 1961) developed a high incidence of pregnancy-independent tumors when infected with horizontally transmitted MMTV (C3H) and pregnancy-dependent tumors which progressed to pregnancy-independence when infected with MMTV(RIII). Even more surprising was the demonstration by Squartini that the virus could increase mammary secretory di erentiation in virgin females and that the intensity of this activity was unique to the strain of MMTV present in the gland (Squartini et al, 1983).…”

Section: Inbred Mouse Strains Having a High Incidence Of Mammary Tumorsmentioning

confidence: 99%

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

2000

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The study of the mouse mammary tumor virus (MMTV) has provided important insights into the mechanisms of gene transcription regulation by steroid hormones, the mode of action of heritable super antigens and the progressive nature of neoplastic transformation in the mammary gland. Here we describe the current situation with respect to the latter aspect of MMTV biology and the prospects for further advance in our understanding of breast cancer in humans that may be expected from a continued study of MMTV-induced mammary neoplasia. MMTV is a heritable somatic mutagen whose target range is limited. Commonly, the tumorigenic capacity of MMTV is restricted to mammary gland, whereas infection is found in a variety of cell types. In order to replicate, proviral DNA must be inserted into the cell DNA and cell division is required to ®x the mutation. Yet only in the mammary epithelium does this lead to neoplastic transformation. This suggests a unique relationship between MMTV and mammary epithelium. In evaluating this relationship, we and others have discovered genes and potential gene pathways that are pertinent in mammary di erentiation and neoplasia. In addition, the clonal nature of these progressive events from normal to malignant phenotype has become increasingly clear. The weight of these observations compel us to conclude that mammary neoplasms arise from multipotent mammary epithelial cells through a process of acquired mutations that are re¯ected in the increasingly malignant nature of the population of progeny produced by these damaged stem cells.

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Section: Inbred Mouse Strains Having a High Incidence Of Mammary Tumorsmentioning

confidence: 99%

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

2000

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“…For example, the epithelium in the mammary gland increases roughly 30-fold each pregnancy only to shrink a like amount following the cessation of lactation during involution (Kordon and Smith, 1998;Nicoll and Tucker, 1965). In all MMTV-infected strains the rate and frequency of mammary tumorigenesis is increased by multiple pregnancy cycles (DeOme et al, 1978a,b;Squartini et al, 1983). This by itself does not completely explain the occurrence of neoplastic transformation in the mammary epithelium because nearly all of the MMTVinfected cells die by apoptosis at involution.…”

Section: Introductionmentioning

confidence: 99%

Reducing mammary cancer risk through premature stem cell senescence

Boulanger

Smith

2001

Oncogene

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The reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. In a study of FVB/ N mice with the transgene, WAP-TGFb1, we discovered that mammary epithelial stem cells were prematurely aged due to ectopic expression of TGF-b1. To test whether premature aging of mammary epithelial stem cells would have an impact on susceptibility or resistance to mammary cancer, female littermates from FVB/ N6WAP-TGF-b1 mating were injected with mouse mammary tumor virus (MMTV) at 8 ± 10 weeks of age. A total of 44 females were inoculated, maintained as breeders and observed for tumor development for up to 18 months. Only one mammary tumor appeared in 17 TGF-b1 females while 15 were collected from 29 wild type sisters. Premalignant mammary epithelial cells in infected glands were identi®ed by transplantation of single cell (1610 5 ) suspensions into nulliparous hosts and testing for hyperplastic outgrowth. Although the number of positive takes was signi®cantly reduced with TGF-b1 cells, both MMTV-infected TGF-b1 and wild type cells produced hyperplastic outgrowths suggesting that premalignant transformation was achieved in each group. The results suggest a positive correlation between the procreative life-span of mammary epithelial stem cells and mammary cancer risk. Oncogene (2001) 20, 2264 ± 2272.

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Molecular and endocrine biomarkers in non-involved breats: Relevance to cancer chemoprevention

1992

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The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro-and rnicronutrients. In the initiation/prornotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistent Ras p21 -GTP binding, altered C16dC2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypicchemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotvpe is suggestive of their potential clinical application in chemopreventive intervention for breast cancer. Q 1992 Wiley-Llss, Inc.

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Early Pathologic Changes in Experimental and Human Breast Cancer: Facts and Comments^a

Cited by 9 publications

References 22 publications

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

Reducing mammary cancer risk through premature stem cell senescence

Molecular and endocrine biomarkers in non-involved breats: Relevance to cancer chemoprevention

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Early Pathologic Changes in Experimental and Human Breast Cancer: Facts and Commentsa

Cited by 9 publications

References 22 publications

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

Reducing mammary cancer risk through premature stem cell senescence

Molecular and endocrine biomarkers in non-involved breats: Relevance to cancer chemoprevention

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Early Pathologic Changes in Experimental and Human Breast Cancer: Facts and Comments^a