SCTR regulates cell cycle-related genes toward anti-proliferation in normal breast cells while having pro-proliferation activity in breast cancer cells
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Kang, Seongeun; Kim, Byungtak; Kang, Han-Sung; Jeong, Gookjoo; Bae, Hansol; Lee, Hyunkyung; Lee, Seungyeon; Kim, Sun Jung
Abstract
Secretin receptor (SCTR), the G-protein coupled receptor (GPCR) for secretin, has been observed to be upregulated in a few tumor types while downregulated in others, promoting or suppressing the proliferation of tumor cells, respectively. However, little is known about the molecular regulatory mechanism of dysregulation in cancer. In the present study, an analysis of the biological pathways affected by methylation in breast cancer using the methylome databases revealed that GPCRs played a major part in the affected pathway. SCTR, one of the dysregulated GPCRs, showed hypermethylation (P<0.01) and downregulation (P<0.05) in breast cancer tissues. Pathway analysis after the downregulation of SCTR by siRNA in MCF-10A cells identified the G2/M stage checkpoint as the top-scored pathway. Cell cycle-related genes were all upregulated or downregulated suppressing cell proliferation. However, the overexpression of SCTR in MCF-7 cells led to a 35% increase of the cell proliferation index and 2.1-fold increase of cellular migration. Our findings indicate that SCTR suppresses the proliferation of normal breast cells, while the gene stimulates the proliferation and migration of cancer cells being downregulated by promoter methylation.
Weld Solidification Cracking in Solid-Solution Strengthened Ni-Base Filler Metals
HOT CRACKING PHENOMENA IN WELDS II
Authors: Lippold, J. C.; Sowards, J. W.; Murray, G. M.; Alexandrov, B. T.; Ramirez, A. J.
Abstract
The weld solidification cracking susceptibility of several solid-solution strengthened Ni-base filler metals was evaluated using the transverse Varestraint test. The alloys tested included Inconel 617, Inconel 625, Hastelloy X, Hastelloy W, and Haynes 230W.* Susceptibility was quantified by determining the solidification cracking temperature range (SCTR) which is a direct measurement of the range over which cracking occurs. This temperature range was then compared to the equilibrium solidification temperature range derived from Calphad-based ThermoCalc (TM) calculations, Scheil-Gulliver solidification simulations, and in-situ measurements using the single sensor differential thermal analysis (SS-DTA) technique. Good correlation among the simulated and measured solidification temperature ranges, and SCTR values were found for the 617 and 230W filler metals. These two filler metals exhibited the best resistance to weld solidification cracking. Correlation among measured and simulated temperature ranges, and SCTR was poor for Hastelloy alloys X and W. Alloy 625 was found to be the most susceptible to solidification cracking, but this result is in conflict with fabrication experience. This appears to be the result of the inability of the Varestraint test to account for crack "healing" during the final stages of solidification.