Characterization of the Region of the Short Arm of Chromosome-8 Amplified in Breast-Carcinoma

Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer, We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGRF1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) focus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (FLAT) genes, Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position, It also showed physical linkage of ANK1 and FLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis

Expression pattern of c-fes oncogene mRNA in human myeloid cells

In this report we explore the relationships between c-fes oncogene product, the process of in vitro myeloid differentation and the responsiveness of myeloid immature cells to GM-CSF by analyzing c-fes mRNA levels in human myeloid populations which were phenotypically and functionally different

Characterization of the Region of the Short Arm of Chromosome-8 Amplified in Breast-Carcinoma

Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer, We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGRF1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) focus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (FLAT) genes, Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position, It also showed physical linkage of ANK1 and FLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis

Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1−/− mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/rasV12 oncoproteins developed bigger tumors than TP53INP1+/+ transformed MEFs or TP53INP1−/− transformed MEFs with restored TP53INP1 expression. Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity