Human Stanniocalcin (STC): Genomic Structure, Chromosomal Localization, and the Presence of CAG Trinucleotide Repeats

Ishibashi, Kenichi, and Masashi Imai. Prospect of a stanniocalcin endocrine/paracrine system in mammals. Am J Physiol Renal Physiol 282: F367-F375, 2002; 10.1152/ajprenal.00364.2000 is a calcium-and phosphate-regulating hormone produced in bony fish by the corpuscles of Stannius, which are located close to the kidney. It is a major antihypercalcemic hormone in fish. As the corpuscles of Stannius are absent, and antihypercalcemic hormones are basically not necessary, in mammals, the discovery of a mammalian homolog, STC1, was surprising and intriguing. STC1 displays a relatively high amino acid sequence identity (ϳ50%) with fish STC. In contrast to fish STC, STC1 is expressed in many tissues, including kidney. More recently, a human gene encoding the second stanniocalcin-like protein, STC2, was identified. STC2 has a lower identity (ϳ35%) with STC1 and fish STC. Similar to STC1, STC2 is also expressed in a variety of tissues. Research into the functions of STCs in mammals is still at an early stage, and the ultimate physiological and pathological roles of STCs have not yet been established. A few studies indicate that STC1, similar to fish STC, stimulates phosphate absorption in the kidney and intestine, but the function of STC2 is still unknown. However, several interesting findings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STCs in mammals. STC1 expression is enhanced by hypertonicity in a kidney cell line or by ischemic injuries and neural differentiation in the brain. STC1 expression in the ovary is also enhanced during pregnancy and lactation. Calcitriol upregulates STC1 and downregulates STC2 expression in the kidney. Interestingly, STC1 and STC2 are expressed in many tumor cell lines, and the expression of STC2 is enhanced by estradiol in breast cancer cells. STC2 is also expressed in pancreatic islets. These results suggest that the biological repertoires of STCs in mammals will be considerably larger than in fish and may not be limited to mineral metabolism. This brief review describes recent progress in mammalian STC research. phosphate transport; calcium homeostasis; hypertonicity; ischemia STANNIOCALCIN (STC; previously named hypocalcin or teleocalcin) is a glycoprotein hormone that was thought to be unique to teleostean and holostean fish (reviewed in Ref. 1). STC is secreted by specialized organs, the corpuscles of Stannius (CS), which are located adjacent to the kidney or scattered throughout the kidney proper. CS cells may be derived from nephric ducts (24). One pair is found in most fish, and the removal of these glands produces hypercalcemia. Therefore, the main function of STC, similar to that of calcitonin, appears to be the prevention of hypercalcemia. In fish, both STC and calcitonin are antihypercalcemic, but the capacity of STC surpasses that of calcitonin. The main targets of STC are the entry routes of Ca: the gills and intestines. In seawate...

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“…The genes for STC1 have been reported in humans, rats, and mice (5,41). They are composed of four exons.…”

Section: Structure Of Stanniocalcin Genesmentioning

confidence: 99%

Prospect of a stanniocalcin endocrine/paracrine system in mammals

Ishibashi

Imai

2002

American Journal of Physiology-Renal Physiology

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“…Stanniocalcin (STC) is a secreted glycoprotein hormone and has two isotypes, STC1 and STC2. Human STC1 is encoded by a single copy gene which is localized at chromosome 8p11.2-p21 (20). STC1 was originally discovered in mammals and in the endocrine glands of the kidneys, and stannius corpuscles of bony fishes (21).…”

Section: Introductionmentioning

confidence: 99%

Klotho inhibits human follicular thyroid cancer cell growth and promotes apoptosis through regulation of the expression of stanniocalcin-1

Dong

Wang

et al. 2015

Oncology Reports

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Abstract.The new anti-aging gene Klotho has been identified as a multi-functional humoral factor which influences multiple biological processes, including tumor progression. Although ample evidence indicates that Klotho plays important roles in cervical, lung and breast cancer, the role and mechanism of Klotho in thyroid cancer are still unclear. The present study aimed to investigate the effects and mechanisms of Klotho in human thyroid cancer cell lines FTC133 and FTC238. Klotho overexpression markedly reduced thyroid cancer FTC133 and FTC238 cell proliferation and enhanced apoptosis, whereas, Klotho silencing in the FTC133 and FTC238 cells increased cell growth. Moreover, soluble human KL1 (sKL) and Klotho overexpression had a similar effect on FTC133 and FTC238 cell growth. A high level of Klotho was also found to be associated with a low level of stanniocalcin 1 (STC1) in both the FTC133 and FTC238 cell lines. STC1 silencing significantly inhibited thyroid cancer cell proliferation, whereas recombinant human STC1 (hSTC1) markedly enhanced cell proliferation. In addition, our study demonstrated that hSTC1 treatment attenuated Klotho-induced inhibition of cell proliferation and promotion of apoptosis. Our data revealed the existence of a moderating effect between Klotho and STC1, where Klotho may inhibit thyroid tumor progression by inhibiting the tumor marker level of STC1. IntroductionThyroid cancer is the most common endocrine malignancy, and the number of new cases diagnosed worldwide has increased in the last decade (1). Thyroid cancer is classified into undifferentiated and differentiated cancer, and the vast majority of thyroid cancers (~80%) are differentiated thyroid cancers (DTCs) (2). DTCs consist of two cellular types: papillary thyroid cancers (PTCs) and differentiated follicular thyroid cancers (FTCs). Various effective treatments have been used for thyroid cancer therapy, such as complete thyroidectomy followed by radioiodine therapy (3). These patients have a low mortality rate and excellent prognosis. However, a subset of patients that develops distant metastases presents with a high disease recurrence rate and poor prognosis and the disease may develop into anaplastic thyroid cancer with a fatal outcome (4,5). Therefore, research on the molecular mechanisms involved in thyroid carcinogenesis will facilitate the development of more effective therapy for this cancer.Ample evidence indicates that aging is the main risk factor for cancer, and most cancers are diagnosed in individuals over 55 years of age (6). Currently, Klotho has recently been identified as a new anti-aging gene and has gained much attention (7). Klotho (KL), a 1012-amino acid type I single-pass transmembrane protein, is widely expressed in various types of tissues, such as brain, kidney, various exocrine and endocrine tissues, including the thyroid gland (8-10). The Klotho gene is composed of 5 exons (8,11) and contains an intracellular domain and an extracellular domain. The extracellular domain of Klotho is composed of two d...

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“…Human STC1 gene is mapped at the metastatic susceptibility locus, 8p, which is known to be related to tumor progression and metastases (Chughtai et al 1999, Macartney-Coxson et al 2008. The identification of the long stretches of CAG repeats in the 5 0 -untranslated region infers the propensity of genetic instability and transcriptional silencing of the gene (Chang et al 1998, Parniewski & Staczek 2002. Our previous study has demonstrated the epigenetic regulation of STC1 gene expression in apoptotic cancer cells treated with histone deacetylase (HDAC) inhibitors (Law et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2

Ching

Yeung

Wong³

2012

Journal of Molecular Endocrinology

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Human stanniocalcin 1 (STC1) has recently been identified as a putative protein factor involved in cellular apoptosis. The use of histone deacetylase inhibitor (i.e. trichostatin A (TSA)) and doxorubicin (Dox) is one of the common treatment methods to induce apoptosis in human cancer cells. A study on TSA and Dox-mediated apoptosis may shed light on the regulation and function of STC1 in cancer treatment. In this study, TSA and Dox cotreatment in human nasopharyngeal carcinoma cells (CNE2) elicited synergistic effects on STC1 gene expression and cellular apoptosis. An activation of p53 (TP53) transcriptional activity in Dox-or DoxCTSA-treated cells was revealed by the increased expression levels of p53 mRNA/protein as well as p53-driven luciferase activities. To elucidate the possible involvement of p53 in STC1 gene transcription, a vector expressing wild-type or dominant negative (DN) p53 was transiently transfected into the cells. Both STC1 promoter luciferase constructs and chromatin immunoprecipitation assays did not support the direct role of p53 in STC1 gene transactivation. However, the synergistic effects of p53 on the induction of NF-kB phosphorylation and the recruitment of acetylated histone H3 in STC1 promoter were observed in TSA-cotreated cells. The overexpression of exogenous STC1 sensitized apoptosis in Dox-treated cells. Taken together, this study provides data to show the cross talk of NF-kB, p53, and histone protein in the regulation of STC1 expression and function.

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Human Stanniocalcin (STC): Genomic Structure, Chromosomal Localization, and the Presence of CAG Trinucleotide Repeats

Cited by 31 publications

References 19 publications

Prospect of a stanniocalcin endocrine/paracrine system in mammals

Prospect of a stanniocalcin endocrine/paracrine system in mammals

Klotho inhibits human follicular thyroid cancer cell growth and promotes apoptosis through regulation of the expression of stanniocalcin-1

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2

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