Disease relevance of Reck

• Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis [1].
• KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days [2].
• This study deals with the growth effect of gastrin on two xenotransplantable human gastric carcinomas (SC-6-JCK, poorly differentiated adenocarcinoma; and St-15, mucinous adenocarcinoma) and on one colonic carcinoma (Co-3, well-differentiated adenocarcinoma) [3].
• BE3333 also showed inhibitory effects against the growth of lung tumors (Lu-65, Lx-1, Lc-1, and Lu-61), stomach tumors (Sc-6 and St-15), and melanoma (SEKI) xenotransplanted into nude mice [4].
• To evaluate the antitumor activity and toxicity of 5-FU and JM-8 in vivo, BALB/cA nu/nu mice bearing human gastric cancer xenografts St-15, St-40 and SC-1-NU were administered 5-FU and JM-8 intraperitoneally [5].

High impact information on Reck

• Cyclic adenosine 3':5'-monophosphate (cAMP)-dependent and cAMP-independent protein kinase activity and the isoenzyme pattern of cAMP-dependent protein kinase were compared in tissues from human nonneoplastic gastric mucosa, 11 human gastric carcinomas, and 2 xenotransplantable human gastric carcinomas (SC-6-JCK and St-15) [6].
• In SC-6-JCK, cyclic adenosine 3':5'-monophosphate (cAMP) in the tumor was increased by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse in nude mice, but such an increase was not observed in St-15 and Co-3 [3].
• Consistent with this finding, the RECK-promoter is activated by MRF4 in cultured cells [1].
• In contrast, a myoblast determination factor MyoD suppresses the RECK-promoter [1].
• The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis [1].

Chemical compound and disease context of Reck

• The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9 [7].

Biological context of Reck

• We have isolated and characterized the 5'-flanking region of the mouse RECK gene aiming to understand the mechanism of oncogene-mediated suppression of RECK gene expression [8].
• Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene [7].
• The molecular mechanisms of the down-regulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered [7].

Anatomical context of Reck

• In the present study, we have found that in later stage wild-type embryos, RECK is abundantly expressed in skeletal muscles, especially in the areas where the myoblast differentiation factor MRF4 is expressed [1].
• Myoblastic cells lacking RECK expression give rise to myotubes at higher efficiency than the cells expressing RECK, indicating that RECK suppresses myotube formation [1].
• We profiled the RNA levels of every MMP, several ADAMs, and inhibitors of metalloproteinases (TIMPs and RECK) in numerous mouse tissues during development and in the uterus during pregnancy [9].
• Mice lacking RECK die in utero with reduced integrity of blood vessels, the neural tube, and mesenchymal tissues [10].

Associations of Reck with chemical compounds

• Additionally, a HDAC inhibitor trichostatin A (TSA) potently antagonized the inhibitory action of ras on RECK [11].
• This was also confirmed in THP or ADM combination chemotherapy with mitomycin C and 5-fluorouracil on St-15 and MKN-45 [12].

Regulatory relationships of Reck

• So, we tested whether ras activation induced the binding of histone deacetylases (HDACs) to Sp1 to repress RECK expression [11].
• The signaling pathway by which ras suppresses RECK was also addressed [11].

Other interactions of Reck

• Co-transfection assay showed that Sp1 and Sp3 are transactivators, rather than repressors, for RECK gene [11].
• Addition of PD98059 or overexpression of dominant-negative mutant of ERK2 indeed reversed ras-mediated inhibition of RECK promoter activity [11].

Analytical, diagnostic and therapeutic context of Reck

• When the same doses of THP and ADM were administered intraperitoneally to nude mice bearing St-15, St-40 and SC-1-NU, the antitumor activity of THP was almost equivalent to ADM in terms of relative mean tumor weight [12].

References