Disease relevance of THRSP

• Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors [1].
• This may explain why primary breast cancers with low S14 do not survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as lymph nodes, and thus do not appear as distant metastases [2].
• S14 but not FAS scores correlated with tumor grade in both DCIS (p=0.003) and invasive cases (p<0.001) [3].

High impact information on THRSP

• In light of these data, we propose a model for fine regulation of human RPS14 transcription that involves RPS14 intron 1 antisense RNAs as positive effectors and S14 protein as a negative effector [4].
• S14 expression provides a pathophysiological link between two prognostic indicators in breast cancer: enhanced lipogenesis and 11q13 amplification [1].
• We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was amplified and expressed in breast cancer-derived cell lines [1].
• A glucose/carbohydrate element has been identified on the L-type pyruvate kinase and spot 14 gene promoters [5].
• For example, fatty acid synthase gene transcription is inhibited by specific polyunsaturated fatty acids; S14 and pyruvate kinase genes contain a specific carbohydrate response element; and editing of apo B-100 to apo B-48 is enhanced by dietary carbohydrate [6].

Chemical compound and disease context of THRSP

• S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth [7].

Biological context of THRSP

• Furthermore, a synteny group of THRSP and its flanking genes [NADH dehydrogenase (NDUFC2) and glucosyltransferase (ALG8)] appears to be conserved among chickens, humans, mice and rats [8].
• Assignment of the "spot 14" gene (THRSP) to human chromosome band 11q13.5 by in situ hybridization [9].
• In the chicken genome, THRSP gene was identified to duplicate into 2 paralogs, THRSPalpha and THRSPbeta [10].
• Thyroid hormone responsive Spot 14 (THRSP) is suggested as a transcription factor involved in the regulation of adipogenic enzymes by 3 thyroid response elements in the promoter region [10].
• We propose that S14 is an acidic transcriptional activator that acts as a homodimer to modulate gene expression as a component of a tripartite complex with a 36-kDa hepatic protein [11].

Anatomical context of THRSP

• In mammals, thyroid hormone responsive Spot 14 (THRSP) is a small acidic protein that is predominately expressed in lipogenic tissue (i.e., liver, abdominal fat and the mammary gland) [8].
• Expression analysis by real-time quantitative PCR showed that THRSP paralogs in ducks were more actively transcribed in fat tissues (i.e., s.c. fat and abdominal fat) than in liver, and the mRNA concentrations of THRSPbeta were higher than that of THRSPalpha in liver and s.c. fat [10].
• Molecular Cloning and Expression of the Duplicated Thyroid Hormone Responsive Spot 14 (THRSP) Genes in Ducks [10].
• In parallel studies, we observed a 36-kDa protein that specifically coimmunoprecipitated with S14 from extracts of radiolabeled rat hepatocytes [11].
• Dytiscus marginalis has a polytrophic ovariole and the maturing oocyte passes through 14 growth stages (S1-S14) [12].

Associations of THRSP with chemical compounds

• Glutathione-S-transferase-S14 and hemagglutinin-S14 fusions copurified from the transfected cells by glutathione-affinity chromatography, indicating their association in vivo [11].
• However, in HepG2 cells, T3 and glucose did not affect the transcription of the human S14 gene [13].
• Compared with mice infected with Luc alone, T3 treatment of mutant TR beta infected mice showed no changes in liver luciferase, weight, or 5'-deiodinase and spot 14 messenger RNA, and the decrease in the serum cholesterol concentration was blunted as in patients with RTH [14].
• Moreover they show that apart from gene amplification there is another steroid-regulated pathway that may enhance Spot 14 expression and lipogenesis in tumor cells [15].

Other interactions of THRSP

• S14 expression in breast tumors is highly concordant with overabundance of a key lipogenic enzyme [16].
• In addition to its responsiveness to thyroid hormone, S14 gene transcription is controlled by dietary substrates, such as glucose and polyunsaturated fatty acids, and by fuel-related hormones including insulin and glucagon [16].

Analytical, diagnostic and therapeutic context of THRSP

• In the current study, cDNA sequences of the duplicated duck THRSP genes were cloned by real-time PCR and rapid amplification of cDNA ends [10].
• In this study we have used immunofluorescence to monitor the intracellular trafficking of epitopically labeled human S14 protein isoforms transiently expressed by cultured Chinese hamster cells [17].
• In the Solanum system the level of the S-RNase messages was analysed by scanning laser densitometry, and it was found that the message levels of the allele S14 declined faster than those coming from S13 in mature flowers [18].
• Low level S14 expression is associated with prolonged disease-free survival in invasive cases, including those with nodal metastasis [3].
• We analyzed 131 breast cancers by immunohistochemistry for S14 and FAS [3].

References