Disease relevance of STC2

• Organ allometry studies show that hSTC-2-induced dwarfism is associated with testicular organomegaly and a significant reduction in skeletal muscle mass likely contributing to the dwarf phenotype. hSTC-2-transgenic mice are also hyperphagic, but this does not result in obesity [1].
• The expression profile of STC2 was further confirmed by in situ hybridization and immunohistochemistry on a larger cohort of 236 unselected breast carcinomas using tissue microarrays [2].
• We conclude that these human fibrosarcoma cells express both STC1 and STC2 as secreted phosphoproteins in vivo, with STC2 being phosphorylated by an ecto-CK2-like enzyme [3].
• Here we report the cloning of a second mammalian stanniocalcin (STC2) from the human osteosarcoma cDNA library [4].
• In addition, STC2 expression is also activated in neuronal cells by oxidative stress and hypoxia but not by several cellular stresses unrelated to the UPR [5].

High impact information on STC2

• In vivo studies revealed that rat cortical neurons rapidly upregulate STC2 after transient middle cerebral artery occlusion [5].
• Expression of STC2 gene is rapidly upregulated in cultured cells after exposure to tunicamycin and thapsigargin, by ATF4 after activation of the ER-resident kinase PERK [5].
• Finally, siRNA-mediated inhibition of STC2 expression renders N2a neuroblastoma cells and HeLa cells significantly more vulnerable to apoptotic cell death after treatment with thapsigargin, and overexpression of STC2 attenuated thapsigargin-induced cell death [5].
• DNA microarray hybridization showed a 3-fold induction of STC2 mRNA expression in MCF-7 cells in < or = 3 h of estrogen exposure and a 3-fold repression in the presence of antiestrogen (one-way ANOVA, P < 0.0005) [2].
• Stanniocalcin 2 is an estrogen-responsive gene coexpressed with the estrogen receptor in human breast cancer [2].

Chemical compound and disease context of STC2

• Two putative paracrine/autocrine factors of potential importance in the regulation of the growth of breast cancer cells were identified to be highly up-regulated by E2: stanniocalcin 2, a calcium/phosphate homeostatic hormone; and inhibin-beta B, a TGF-beta-like factor [6].

Biological context of STC2

• We speculate that STC2 may play a role in glucose homeostasis [7].
• The STC2 gene was localized to human chromosome 5q35 [7].
• We purified both the native hamster and recombinant human STC2 proteins and obtained a partial amino acid sequence of the hamster protein [7].
• The function of STC-2 has not been examined; thus we generated two lines of transgenic mice overexpressing human (h)STC-2 to gain insight into its potential functions through identification of overt phenotypes [1].
• Consequently, similar to STC-1, STC-2 can act as a potent growth inhibitor and reduce intramembranous and endochondral bone development and skeletal muscle growth, implying that these tissues are specific physiological targets of stanniocalcins [1].

Anatomical context of STC2

• In cultured granulosa cells, treatment with human or fish STC2 suppressed FSH-induced progesterone, but not estradiol or cAMP, production [8].
• Northern blot analysis revealed that the primary site of human STC2 production is the pancreas, and immunostaining localized the STC2 protein to a subpopulation of cells in the islet [7].
• We examined a human fibrosarcoma cell line, HT1080, that has high steady-state STC1 and STC2 mRNA levels, to determine whether these proteins are secreted [3].
• Stanniocalcin 2: characterization of the protein and its localization to human pancreatic alpha cells [7].
• STC2 is also expressed in pancreatic islets [9].

Associations of STC2 with chemical compounds

• Thus, STC2 is a functional homodimeric glycoprotein, and thecal cell-derived STC2 could play a paracrine role during follicular development [8].
• The STC2 suppression of progesterone production was associated with the inhibition of FSH-induced CYP11A and 3beta-hydroxysteroid dehydrogenase expression [8].
• The second homologue (STC2) is 30-38% identical to the fish stanniocalcins, and is characterized by unique cysteine and histidine motifs that are not found in the other stanniocalcins [7].
• The in vitro CK2 phosphorylation site was shown by matrix-assisted laser-desorption ionization-time-of-flight MS to be a single serine located between Ser-285 and Ser-298 in the C-terminal region of STC2 [3].
• When Atlantic salmon glands were fractionated by concanavalin A (ConA)-Sepharose chromatography, two distinct forms of the hormone were identified, both of which were recognized by sockeye salmon STC antiserum, and designated as STC1 and STC2 [10].

Other interactions of STC2

• Based on the prominent expression of mammalian STC1 in the ovary, we tested STC2 expression in rat ovary and the regulation of STC2 expression by gonadotropins [8].
• Following incubation of HT1080 cells with (32)P, labelled STC1 and STC2 were found to be secreted into the medium [3].
• Chromosomal localization of two human genes involved in phosphate homeostasis: the type IIb sodium-phosphate cotransporter and stanniocalcin-2 [11].

Analytical, diagnostic and therapeutic context of STC2

• In situ hybridization studies also revealed that STC2 is expressed in thecal cell layers of antral and preovulatory follicles after gonadotropin stimulation [8].
• Real-time PCR analyses also demonstrated that STC2 is expressed mainly in thecal layers [8].
• Molecular cloning of a second human stanniocalcin homologue (STC2) [4].
• Sequence analyses revealed a high sequence similarity of the chicken STC (cSTC) clone to mammalian STC2 [12].
• Embryo transfer experiments further confirmed that STC-1 and STC-2 expression at the implantation sites was induced by the implanting blastocyst [13].

References