PMID- 9620446 OWN - NLM STAT- MEDLINE DCOM- 19980807 LR - 20061115 IS - 0145-5680 (Print) IS - 0145-5680 (Linking) VI - 44 IP - 3 DP - 1998 May TI - The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos oncogenes in vitro and is spontaneously metastatic in vivo. PG - 493-504 AB - IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative human breast cancer cell line previously established in our laboratory from a patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To further characterize these systems, immunocytochemical analysis was performed for differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous in these different systems. Previously reported karyotypic analysis has shown extensive chromosomal alterations including double min. Searching for oncogene amplification, we detected augmented copy number of c-myc and c-fos, the last one with two rearranged fragments. No amplification was found for c-erbB-2 in the cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the patient's primary tumor DNA. The differences observed between the patient's tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal expansion of cell variants not present in the original tumor. Electron microscopy of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense granules, presumably secretory, distributed all over the cytoplasm and great nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of invading cells by Matrigel assay. After nearly 40 sequential subcutaneous passages of the original xenograft through nude mice, 80% of recipients developed spontaneous metastases, primarily to the lung and lymph nodes. Since this experimental model allowed to analyze changes produced in cancer cells from the primary tumor during adaptation to in vitro and in vivo growth, our results provide novel insights on the behaviour of hormone independent metastatic breast cancer. FAU - Bover, L AU - Bover L AD - Instituto de Investigaciones Bioquimicas Fundacion Campomar, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. FAU - Barrio, M AU - Barrio M FAU - Bravo, A I AU - Bravo AI FAU - Slavutsky, I AU - Slavutsky I FAU - Larripa, I AU - Larripa I FAU - Bolondi, A AU - Bolondi A FAU - Ayala, M AU - Ayala M FAU - Mordoh, J AU - Mordoh J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Cell Mol Biol (Noisy-le-grand) JT - Cellular and molecular biology (Noisy-le-Grand, France) JID - 9216789 RN - 0 (Antigens, Neoplasm) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (Receptors, Estrogen) SB - IM MH - Animals MH - Antigens, Neoplasm/biosynthesis MH - Breast Neoplasms MH - Carcinoma, Ductal, Breast MH - Female MH - Gene Amplification MH - Humans MH - Mice MH - Mice, Nude MH - Neoplasm Invasiveness MH - Proto-Oncogene Proteins c-fos/*genetics MH - Proto-Oncogene Proteins c-myc/*genetics MH - Receptors, Estrogen/genetics MH - Transplantation, Heterologous MH - Tumor Cells, Cultured EDAT- 1998/06/10 00:00 MHDA- 1998/06/10 00:01 CRDT- 1998/06/10 00:00 PHST- 1998/06/10 00:00 [pubmed] PHST- 1998/06/10 00:01 [medline] PHST- 1998/06/10 00:00 [entrez] PST - ppublish SO - Cell Mol Biol (Noisy-le-grand). 1998 May;44(3):493-504.