Syngeneic mouse mammary carcinoma cell lines: Two closely related cell lines with divergent metastatic behavior

Department of Medical Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Clinical and Experimental Metastasis (Impact Factor: 3.49). 02/2005; 22(1):47-59. DOI: 10.1007/s10585-005-2908-5
Source: PubMed


Two cell lines, Met-1fvb2 and DB-7fvb2, with different metastatic potential, were derived from mammary carcinomas in FVB/N-Tg(MMTV-PyVmT) and FVB/N-Tg(MMTV-PyVmT

) mice, transplanted into syngeneic FVB/N hosts and characterized. The lines maintain a stable morphological and biological phenotype after multiple rounds of in vitro culture and in vivo transplantation. The Met-1fvb2 line derived from a FVB/N-Tg(MMTV-PyVmT) tumor exhibits invasive growth and 100% metastases when transplanted into the females FVB/N mammary fat pad. The DB-7fvb2 line derived from the FVB/N-Tg(MMTV-PyVmT

) with a “double base” modification at Y315F/Y322F exhibits more rapid growth when transplanted into the mammary fat pad, but a lower rate of metastasis (17%). The Met1fvb2 cells show high activation of AKT, while DB-7fvb2 cells show very low levels of AKT activation. The DNA content and gene expression levels of both cell lines are stable over multiple generations. Therefore, these two cell lines provide a stable, reproducible resource for the study of metastasis modulators, AKT molecular pathway interactions, and gene target and marker discovery.

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    • "Unlike human tumors, the mouse tumors generated in our mouse populations all result from the expression of polyoma middle T antigen, driven from the mouse mammary tumor virus enhancer and promoter. In addition, comparative genome hybridization [27] and spectral karyotyping [28] indicate that the genome of mouse PyMT tumors are much more stable than human tumors, likely reducing any contribution of somatic mutation to the observed expression profiles. Furthermore, while we cannot definitively rule out the possibility that varying the genetic background of the host might alter the transcriptional patterns of the transgene, there is no evidence at present to support this possibility. "
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    ABSTRACT: Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer.
    PLoS ONE 08/2013; 8(8):e72287. DOI:10.1371/journal.pone.0072287 · 3.23 Impact Factor
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    • "The MVT1 murine mammary carcinoma cell line was derived from an explant tumor culture from MMTV-c-Myc/Vegf transgenic mice (27). Met1 murine mammary tumor cells were derived from MMTV-Polyoma virus middle T antigen (PyVmT) transgenic mice (28). Met1 and MVT1 cells were cultured as previously described (9,14). "
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    ABSTRACT: Endogenous hyperinsulinemia and insulin receptor (IR)/ insulin-like growth factor-1 receptor (IGF-1R) phosphorylation in tumors are associated with a worse prognosis in women with breast cancer. In vitro, insulin stimulation of the IR increases proliferation of breast cancer cells. However, in vivo studies demonstrating that IR activation increases tumor growth, independent of IGF-1R activation are lacking. We hypothesized that endogenous hyperinsulinemia increases mammary tumor growth by directly activating the IR rather than the IGF-1R or hybrid receptors. We aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independent of IGF-1R signaling. We induced orthotopic mammary tumors in control FVB/n and hyperinsulinemic MKR mice and treated them with the insulin analog AspB10, rhIGF-1 or vehicle. Tumors from mice with endogenous hyperinsulinemia were larger and had greater IR phosphorylation, but not IGF-1R phosphorylation than those from control mice. Chronic AspB10 administration also increased tumor growth and IR (but not IGF-1R) phosphorylation in tumors. IGF-1 led to activation of both the IGF-1R and IR and probably hybrid receptors. Our results demonstrate that IR phosphorylation increases tumor growth, independently of IGF-1R / hybrid receptor phosphorylation and warrant consideration when developing therapeutics targeting the IGF-1R, but not the IR.
    Diabetes 07/2013; 62(10). DOI:10.2337/db13-0249 · 8.10 Impact Factor
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    • "Mice consumed the experimental diets for 3 months before syngeneic orthotopic transplantation of 1!10 5 Met1 mammary tumor cells into the fourth mammary fat pad. The Met1 cell line (a gift from Dr William Mueller) was originally derived from mammary carcinomas in FVB/N-Tg (MMTV-PyVmT) mice (Borowsky et al. 2005), and was maintained in complete media (low glucose DMEM, supplemented with 10% fetal bovine serum, penicillin– streptomycin and glutamine) at 37 8C in a humidified 5% CO 2 incubator. In preparation for transplantation, cells were washed with PBS, trypsinized, and viable cells were quantified by trypan blue exclusion using a hemacytometer (Fisher Scientific, Waltham, MA, USA). "
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    ABSTRACT: Luminal breast tumors with little or no estrogen receptor-α expression confer poor prognosis. Using the Met1 murine model of luminal breast cancer, we characterized the insulin-like growth factor 1 (IGF1)-dependency of diet-induced obesity (DIO) and calorie restriction (CR) effects on tumor growth, growth factor signaling, epithelial-to-mesenchymal transition (EMT) and chemokine expression. Liver-specific IGF1-deficient (LID) and littermate control (LC) mice were administered control, DIO or 30% CR diets for 3 months before orthotopic injection of Met1 cells. Tumors grew for 1 month, were excised and assessed for Akt pathway activation and mRNA expression of chemokine and EMT constituents. LID mice, regardless of diet, displayed reduced Met1 tumor growth and downregulated Akt, EMT and chemokine pathways. CR, relative to control, reduced serum IGF1 and Met1 tumor growth in LC (but not LID) mice. DIO, relative to control, increased Met1 tumor growth and chemokine expression in LID mice, and had no effect on serum IGF1 or pAkt or cyclin D1 expression in either genotype. Thus, circulating IGF1 (in association with Akt, EMT and chemokines) regulated Met1 tumor growth. While the anticancer effects of CR were largely IGF1-dependent, the procancer effects of DIO manifested only when circulating IGF1 levels were low. Thus, in a murine model of luminal breast cancer, IGF1 and its downstream signaling pathway, EMT and chemokines present possible mechanistic regulatory targets. Transplanted MMTV-1 Wnt1 mammary tumor growth was also reduced in LID mice, relative to LC mice, suggesting the IGF1 effects on mammary tumor growth are not limited to Met1 tumors.
    Endocrine Related Cancer 11/2012; 20(1). DOI:10.1530/ERC-12-0329 · 4.81 Impact Factor
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