RESUMEN
Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.
Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Neoplasias Pancreáticas/metabolismo , Zinc/metabolismo , Proteínas de Transporte de Catión/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Conductos Pancreáticos/metabolismo , Regulación hacia ArribaRESUMEN
Pancreatic cancer is a multiple genetic disorder with many mutations identified during the progression. Two mouse pancreatic cancer cell lines were established which showed different phenotype in vivo: a non-metastatic cell line, Panc02, and a highly metastatic cell line, Panc02-H7, a derivative of Panc02. In order to investigate whether the genetic mutations of key genes in pancreatic cancer such as KRAS, TP53 (p53), CDKN2A (p16), SMAD4, ZIP4, and PDX-1 contribute to the phenotypic difference of these two mouse pancreatic cancer cells, we sequenced the exonic regions of these key genes in both cell lines and in the normal syngeneic mouse pancreas and compared them with the reference mouse genome sequence. The exons of KRAS, SMAD4, CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes were amplified and the genotype of these genes was determined by Sanger sequencing. The sequences were analyzed with Sequencher software. A mutation in SMAD4 was identified in both cell lines. This homozygote G to T mutation in the first position of codon 174 (GAA) generated a stop codon resulting in the translation of a truncated protein. Further functional analysis indicates that different TGF-ß/SMAD signaling pathways were involved in those two mouse cell lines, which may explain the phonotypic difference between the two cells. A single nucleotide polymorphism (SNP) in KRAS gene (TAT to TAC at codon 32) was also identified in the normal pancreas DNA of the syngenic mouse and in both derived tumoral Panc02 and Panc02-H7 cells. No mutation or SNP was found in CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes in these two cell lines. The absence of mutations in genes such as KRAS, TP53, and CDKN2A, which are considered as key genes in the development of human pancreatic cancer suggests that SMAD4 might play a central and decisive role in mouse pancreatic cancer. These results also suggest that other mechanisms are involved in the substantial phenotypic difference between these two mouse pancreatic cancer cell lines. Further studies are warranted to elucidate the molecular pathways that lead to the aggressive metastatic potential of Panc02-H7.
Asunto(s)
Neoplasias Pancreáticas/genética , Análisis de Secuencia de ADN/métodos , Animales , Línea Celular Tumoral , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Proteínas de Homeodominio/genética , Ratones , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Transactivadores/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Conical ring emission from a short-cavity dye laser has been observed and modeled as Kastler rings, that is, the high-angle emission modes of a plano-plano (Fabry-Perot) laser cavity in agreement with the predictions made 31 years ago by Kastler [Appl. Opt. 1, 17 (1962)]. The excitation of the discrete rings is due to a transfer of energy from the axial modes rather than to spontaneous emission. The mechanism for energy transfer is argued to be scattering of light from imperfections on the mirror surfaces.
RESUMEN
The statistics of turn-on delay times for a longitudinal mode and the total intensity from a multimode, standing-wave, short-cavity dye laser are measured and compared with numerical simulations of a multimode theory of laser dynamics. Differences between the measurements and the theory for the average and standard deviation of the turn-on time are due to transitory modes that decay as a result of frequency-dependent losses and gains. Associated with this phenomenon is a kink in the time evolution of the mode intensity that represents a transition in the dynamics from domination by independent growth of all modes to domination by competition between modes with differing net gains. This unequal competition increases the average and standard deviation of the mode turn-on time.
