First Author | Jacquemart IC | Year | 2009 |
Journal | Int J Oncol | Volume | 34 |
Issue | 2 | Pages | 517-28 |
PubMed ID | 19148488 | Mgi Jnum | J:156981 |
Mgi Id | MGI:4422160 | Citation | Jacquemart IC, et al. (2009) Rassf3 is responsible in part for resistance to mammary tumor development in neu transgenic mice. Int J Oncol 34(2):517-28 |
abstractText | MMTV/neu transgenic mouse line is a well-documented model for studying HER2/neu-related breast cancer. Approximately 80% of these mice develop mammary tumors by 11 months of age, whereas a small percentage appears to have naturally acquired resistance to HER2/neu tumorigenesis. To identify factors responsible for tumor resistance in these transgenic mice, comparative genetic profiling was used to screen alterations in gene expression in the mammary gland. A novel gene, the RAS association domain (RalGDS/AF-6) family 3 (Rassf3), which belongs to a family of RAS effectors and tumor suppressor genes, was identified. Data indicated 1) that Rassf3 is overexpressed in mammary gland of tumor-resistant MMTV/neu mice compared to tumor-susceptible MMTV/neu littermates or non-transgenic mice, and 2) Rassf3 is significantly up-regulated in neu-specific mouse mammary tumors compared to adjacent normal tissues. In vitro overexpression of RASSF3 inhibited cell proliferation in HER2/neu positive human and mouse breast cancer cell lines, possibly through induction of apoptosis. A novel MMTV/Rassf3-neu bi-transgenic mouse line, overexpressing Rassf3 and neu genes in mammary glands, was established. Mammary tumor incidence in bi-transgenic mice was delayed compared to their MMTV/neu+/- littermates. These data suggest that Rassf3 may influence mammary tumor incidence in MMTV/neu transgenic mice. |