Two cell lines, Met-1(fvb2) and DB-7(fvb2), with different metastatic potential, were derived from mammary carcinomas in FVB/N-Tg(MMTV-PyVmT) and FVB/N-Tg(MMTV-PyVmT ( Y315F/Y322F )) 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-1(fvb2) 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-7(fvb2) line derived from the FVB/N-Tg(MMTV-PyVmT ( Y315F/Y322F )) 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 Met1(fvb2) cells show high activation of AKT, while DB-7(fvb2) 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.

IntroductionBreast cancer is among the most common human cancers, affecting one in every eight women and accounting for an estimated 192,000 cases and more than 40,000 deaths in the United States during 2001. One of the significant predictors of breast cancer prognosis is regional and distant metastasis; yet the mechanism of metastasis and the ability to predict it are far from being fully understood.From both a clinical and experimental perspective, a more detailed understanding of the mechanisms of metastasis is needed in order to identify better diagnostic markers and therapeutic approaches.In order to study breast cancer, many investigators have used human derived cell lines that have yielded significant insight into the biology of breast cancer; yet these models DMEM = Dulbecco's modified Eagle medium; EDTA = ethylenediamine tetraacetic acid; FBS = fetal bovine serum; H&E = hematoxylin and eosin; MAPK = mitogen-activated protein kinase; mT = middle T; OPN = osteopontin; PBS = phosphate-buffered saline; PCR = polymerase chain reaction; PI3-K = phosphatidylinositol-3-kinase; PyV = polyomavirus; SEM = scanning electron microscopy; SSH = suppression subtractive hybridization. AbstractIntroduction: In order to study metastatic disease, we employed the use of two related polyomavirus middle T transgenic mouse tumor transplant models of mammary carcinoma (termed Met and Db) that display significant differences in metastatic potential.

Introduction Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene.

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