Relevance of chromosome 4 in a murine model of breast cancer progression

MARÍA B PAMPENA; CLAUDIA LANARI; VICTORIA T FABRIS

San Francisco

Conferencia; AACR Advances in Breast Cancer Resarch: Genetics, Biology and Clinical Application Conference; 2011

AACR

C4-HD is a hormone dependent (HD) mammary carcinoma induced by medroxyprogesterone acetate (MPA) which has a near diploid modal chromosome number (normal mouse karyotype 2n=40) and four translocations, one of them involving chromosome 4. We are interested in this chromosome since several tumors of our model show chromosome aberrations involving chromosome 4. We have also shown that hormone independent (HI) variants may maintain the diploid chromosome number of the HD tumor or increase their modal number, suggesting that hormone independence is not necessarily related to an increase in chromosome number. The aim of this work was to study the presence of chromosome 4 alterations in two different HI tumor variants derived from C4-HD. In addition, we focused on studying the karyotype of the diploid CC4-3-HI tumor through different passages, to investigate if successive in vivo transplants will eventually lead to a polyploid karyotype. Metaphases and nuclei from primary cultures of HI tumors were analyzed by G-banding and Fluorescence in situ Hybridization (FISH). Previous studies carried out on C4-HI and CC4-3-HI showed that both HI variants presented gain in copy number of the region proximal to the centromere of chromosome 4. FISH analysis of two new HI variants originated (C4-3-HI and C4-4-HI) revealed most of the cells with four or more copies of the proximal region of chromosome 4 (67% and 83%, respectively), and a triploid chromosome number in both HI tumors. CC4-3-HI tumor showed even after 70 syngeneic transplantations (approximately eight years of continuous passages) the same karyotype, including the same chromosome translocations observed in C4-HD tumor. Hormone independent tumors can maintain the HD karyotype through several passages, or can lose the translocations of the parental tumor. However, all of them show alterations involving chromosome 4, indicating that this chromosome may be relevant during the progression of murine luminal mammary carcinomas.