Rassf3 is responsible in part for resistance to mammary tumor development in neu transgenic mice.
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.
Jacquemart
Isabelle C
IC
Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
Springs
Alison E B
AE
Chen
Wen Y
WY
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; C454041:RASSF3 protein, human; D020559:Monomeric GTP-Binding Proteins