International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 158 - GENETIC STUDIES ABOUT MAMMARY TUMOR METASTATIC PROGRESSION IN MOUSE

Y-G Park
LPG/CCR/NCI/NIH

1) Lyu M-S, 2) Montagna C, 1) Lukes L, 3) Ried T, 1) Hunter KW
1) LPG/CCR/NCI/NIH, 2) MB/ NCI/NIH, 3) GB/ NCI/NIH

The ability of a tumour to metastasize is the major determinant of cancer-patient mortality. Therefore elucidation of the metastasis pathway is an important priority for cancer biology. Studies have demonstrated that tumour progression from normal epithelium to metastastic cell is a complex multi-step process with many different barriers for a tumor to successfully colonize a distant site.  To further explore the molecular and genetic events required for tumor dissemination, our laboratory uses the highly metastatic MMTVPyMT634Mul transgenic mouse mammary tumor model.  LOH and cytogenetic analysis has demonstrated unlike human solid tumors, the tumors of this mouse model are diploid or near-diploid, with few translocations or chromosomal aberrations.  We have taken advantage of this low level of genomic instability to search for specific genomic changes associated with metastatic progression.  Using matched primary and metastatic tumor cell cultures representational difference analysis (RDA) has been performed.  A number of the products have been demonstrated to lie near genes previously associated with metastatic progression.  In addition, microarray analysis has demonstrated that genes associated with the RDA products are highly differentially expressed between high and low metastatic-potential inbred strains of mice.   These data suggest that the genes associated with the RDA products may play important roles in tumor metastasis and further investigations are planned to explore the possibilities.


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