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.
Ambartsumian
N S
NS
Danish Cancer Society, Department of Molecular Cancer Biology, Copenhagen, Denmark.
Grigorian
M S
MS
Larsen
I F
IF
Karlstrøm
O
O
Sidenius
N
N
Rygaard
J
J
Georgiev
G
G
Lukanidin
E
E
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D002135:Calcium-Binding Proteins; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; D005346:Fibroblast Growth Factors