TY - JOUR
T1 - Cytogenetic findings, Trp53 mutations, and hormone responsiveness in a medroxyprogesterone acetate induced murine breast cancer model
AU - Fabris, Victoria T.
AU - Benavides, Fernando
AU - Conti, Claudio
AU - Merani, Susana
AU - Lanari, Claudia
N1 - Funding Information:
This work was supported by Fundación Sales (Specific Grant 2000-2002) and by SECyT (PICT 99 No. 05-06389) from Argentina and by NIEHS grant ES007784. We are grateful to Miss J. Bolado for excellent technical assistance in animal care, to the Molecular Biology Facility Core at Science Park for DNA sequencing, to Dr. C.M. Aldaz for kindly providing the mouse probes for FISH, and to Dr. C.D. Pasqualini for reviewing the manuscript.
PY - 2005/9
Y1 - 2005/9
N2 - Medroxyprogesterone acetate (MPA)-induced mammary carcinomas express high levels of estrogen (ER) and progesterone receptors (PR) and when transplanted in syngeneic mice they show a progestin-dependent (PD) growth pattern. By successive transplantation, progestin-independent (PI) variants were generated and showed a different response to antihormone therapy. A diploid chromosome number (2n = 40) was found in three of five PD tumors, with numbers in the triploid to tetraploid range in the other two. Some PI tumors were diploid, but most were aneuploid (8 of 12 tumors). The most frequent alterations found in PD and PI tumors were gains of chromosomes 3, 4, and 6 and losses of chromosomes 16 and X. Chromosomes 4 and 7 were involved in translocations in three of the four tumor families studied. single-strand conformation polymorphism analysis revealed a point mutation on the Trp53 gene in one of the PD tumors; this showed a stable diploid karyotype, suggesting that mutated Trp53 is not uniquely involved in chromosome instability. We have shown that hormone independence may be acquired without changes in ploidy, suggesting that the increase in ploidy is favored by successive transplantation. In our model, diploid tumors responded to hormone treatment but aneuploid tumors were either responsive or not.
AB - Medroxyprogesterone acetate (MPA)-induced mammary carcinomas express high levels of estrogen (ER) and progesterone receptors (PR) and when transplanted in syngeneic mice they show a progestin-dependent (PD) growth pattern. By successive transplantation, progestin-independent (PI) variants were generated and showed a different response to antihormone therapy. A diploid chromosome number (2n = 40) was found in three of five PD tumors, with numbers in the triploid to tetraploid range in the other two. Some PI tumors were diploid, but most were aneuploid (8 of 12 tumors). The most frequent alterations found in PD and PI tumors were gains of chromosomes 3, 4, and 6 and losses of chromosomes 16 and X. Chromosomes 4 and 7 were involved in translocations in three of the four tumor families studied. single-strand conformation polymorphism analysis revealed a point mutation on the Trp53 gene in one of the PD tumors; this showed a stable diploid karyotype, suggesting that mutated Trp53 is not uniquely involved in chromosome instability. We have shown that hormone independence may be acquired without changes in ploidy, suggesting that the increase in ploidy is favored by successive transplantation. In our model, diploid tumors responded to hormone treatment but aneuploid tumors were either responsive or not.
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U2 - 10.1016/j.cancergencyto.2005.02.008
DO - 10.1016/j.cancergencyto.2005.02.008
M3 - Article
C2 - 16102583
AN - SCOPUS:23644458321
SN - 0165-4608
VL - 161
SP - 130
EP - 139
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 2
ER -