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Results for “MAMMARY NEOPLASMS, EXPERIMENTAL”

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At least 217 records · Page 12Linked to original sources
PubMed2003

Modeling human breast cancer metastasis in mice: maspin as a paradigm.

Breast cancer is the most common cancer detected in women, accounting for nearly one out of every three cancers diagnosed in the United States. Most cancer patients do not die from the primary tumor but die due to metastasis. Therefore, the study of metastasis is of most importance both to the clinician and patient. In the past, animal models have been used in breast cancer research and mammary gland biology. Our group has also established several animal models to address the function of a novel tumor suppressor gene maspin in breast tumor progression. Maspin was initially isolated from normal mammary epithelial cells. Its expression was down regulated in breast tumors. To test the protective role of maspin overexpression in mammary tumor progression, we crossed maspin overexpression transgenic mice (WAP-maspin) with a strain of oncogenic WAP-SV40 T antigen mice. The bitransgenic mice had reduced tumor growth rate and metastasis. Maspin overexpression increased the rate of apoptosis of both preneoplastic and carcinomatous mammary epithelial cells. Maspin reduced tumor growth through a combination of reduced angiogenesis and increased apoptosis. In a separate animal experiment, maspin overexpressing mammary tumor cells (TM40D) were implanted into the fat pad of syngeneic mice. TM40D tumor cells were very invasive and metastatic. However, both primary tumor growth and metastasis were significantly blocked in TM40D cells that overexpress maspin as a consequence of plasmid or retrovirus infection. These evidences demonstrate that maspin function to inhibit primary tumor growth as well as invasion and metastasis. Elucidating the molecular mechanism of maspin action will shed light on our understanding of breast cancer invasion and metastasis.

Animals↗
PubMed2001

Transgenic Polyoma middle-T mice model premalignant mammary disease.

Mice transgenic for the Polyomavirus middle T (PyV-mT) gene have been widely used to study mammary tumorigenesis and metastasis. Although numerous molecular insights were gained from the analysis of these transgenic malignant tumors, the early events leading to malignant transformation have not been systematically investigated nor has the biological potential of hyperplastic lesions been documented. This paper presents the first comprehensive histopathological characterization of transgenic PyV-mT hyperplasias together with classical transplantation experiments designed to test the growth potential of these lesions. Moreover, stable hyperplastic outgrowth lines were established as a tool to study premalignant PyV-mT-induced hyperplasias in detail. Each line has a different tumor latency, indicating that PyV-mT-induced hyperplasias, like early proliferative lesions seen in the human breast, are heterogeneous with respect to their malignant potential. Our results settle a controversy; they establish that PyV-mT gene expression alone is insufficient to induce tumors and that additional events are required for tumorigenesis and metastasis. These results support the use of PyV-mT transgenic mice as a model for investigating the multistep progression of malignant mammary tumorigenesis and metastasis.

Animals↗
PubMed1990

Association of hst gene expression with metastatic phenotype in mouse mammary tumors.

From the pregnancy-dependent mouse mammary tumor TPDMT-4, four autonomous sublines were established after its independent progression under different conditions. Despite their similar growth rates in inguinal fat pads, three sublines formed lung metastases, and one did not when they were injected i.v. into mice as a single cell suspension. The TPDMT-4 tumor and the nonmetastatic subline expressed mRNA for the orf gene of mouse mammary tumor virus, whereas all metastatic sublines did not. This suggested that the loss of its expression may have been a prerequisite for the progression toward metastatic ability. To identify the gene(s) participating in the generation and the progression of TPDMT-4, the expression of 23 different oncogenes was analyzed. The expression of int-2 was detected in TPDMT-4 and in all sublines, indicating that TPDMT-4 was generated by activation of this gene, whereas hst expression occurred only in the metastatic sublines. These results demonstrated that the hst gene may contribute to tumor progression from a nonmetastatic to a metastatic phenotype in the mouse mammary tumor system.

Adipose Tissue↗
PubMed1989

Unique male mammary tumors developing in the inbred soft-furred field rats Millardia meltada.

Inbred lines of the soft-furred rat, Millardia meltada, were studied with special reference to spontaneous male mammary tumors. Adult males had the hyperplastic, pigmented inguinal mammary tissues and frequently developed bilateral mammary tumors. The tumors, no longer pigmented, were histologically well-differentiated adenocarcinomas associated with the myoepithelial cells and showed a variety of growth patterns depending on the stage of progression. They were transplantable to male, but not to female or castrated male nude mice. A significant number of androgen as well as estrogen binding sites were demonstrated in the nuclei of the transplanted tumor cells by in situ autoradiography. Neither virus particle nor mouse mammary tumor virus-specific antigen expression was detected in the tumor cells by electron microscopic and immunohistochemical studies. Normal females were generally free of pigment and tumor, although the androgen treatment induced marked pigmentation (deposit of nonfluorescent lipofuscin and hemosiderin) and hyperplasia of the female mammary epithelial cells, without a tumor. Possible relationships between pigmentation and tumor development were considered.

Animals↗
PubMed1994

Mammary tumorigenesis and metastasis in transgenic mice.

The transgenic mouse has emerged as an important model system to assess the transforming potential of oncogenes in the mammary epithelium. Mammary gland-specific expression of oncogenes in transgenic mice has resulted in the induction of a variety of phenotypes ranging from benign epithelial hyperplasias to metastatic mammary tumors. The induction of tumors in most of these transgenic models is a multi-step process where transgene expression, although required, is not sufficient for conversion of the primary mammary epithelial cell to the transformed phenotype. While the identity of many of these collaborating genetic events is obscure, several approaches have been applied with might shed light on their nature. In a few exceptional transgenic strains, tumor progression can occur very rapidly suggesting that, if additional genetic events are required, they occur very frequently. Recent genetic and biochemical characterization of these strains offers insight into the molecular mechanisms that may underlie the complex phenotypic features exhibited by these transgenic strains.

Animals↗
PubMed1996

Metastasis of mammary carcinomas in GRS/A hybrid mice transgenic for the mts1 gene.

Transgenic mice, carrying the mts1 gene, one of the genes involved in the acquisition of the metastatic phenotype, were generated. The mts1 gene was placed under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) promoter leading to overexpression in the lactating mammary gland of transgenic animals. Animals bearing the transgene appear phenotypically normal. Animals of two transgenic lines (Tg463 and Tg507) were crossed with the GRS/A mice. The GRS/A strain is characterized by high incidence of mammary tumors which rarely metastasize. 40% of the tumor bearing hybrid GRS/A mts1 females were found to develop secondary tumors in the lungs. The Mts1 protein was detected in the transgene primary tumor cells as well as in the corresponding metastases. Nontransgenic littermates expressed the Mts1 protein only in the stromal cells surrounding the tumor but not in the tumor cells by itself. Taken together these observations indicate that overexpression of the mts1 gene in the mouse mammary carcinoma cells gives rise to more aggressive tumors which are able to metastasize.

Animals↗
PubMed1996

Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours.

Increased levels of S100A4 (p9Ka) confer metastatic ability on a normally non-metastatic epithelial cell line. To find out whether S100A4 can induce metastasis in vivo, transgenic mice expressing high levels of S100A4, but which show no phenotypic effect, have been mated with MMTV-neu transgenic mice which succumb to stochastic mammary neoplasia related to expression of the MMTV-neu transgene. Resultant bitransgenic, multiparous, female progeny expressing both S100A4 and Neu have a slightly earlier incidence of palpable mammary tumours than the MMTV-neu offspring and specifically exhibit macroscopic metastatic lesions in the lungs. The S100A4 transgene is expressed in primary and secondary lesions of bitransgenic offspring and its expression is particularly associated with regions of invasion of primary lesions and metastases.

Animals↗