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Gene Review

THRSP  -  thyroid hormone responsive

Homo sapiens

Synonyms: LPGP1, Lpgp, S14, SPOT14, Spot 14 protein, ...
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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


Biological context of THRSP


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].


  1. The "Spot 14" gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: implications for control of tumor metabolism. Moncur, J.T., Park, J.P., Memoli, V.A., Mohandas, T.K., Kinlaw, W.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Spot 14: A marker of aggressive breast cancer and a potential therapeutic target. Kinlaw, W.B., Quinn, J.L., Wells, W.A., Roser-Jones, C., Moncur, J.T. Endocrinology (2006) [Pubmed]
  3. Expression of "Spot 14" (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker. Wells, W.A., Schwartz, G.N., Morganelli, P.M., Cole, B.F., Gibson, J.J., Kinlaw, W.B. Breast Cancer Res. Treat. (2006) [Pubmed]
  4. Regulation of human RPS14 transcription by intronic antisense RNAs and ribosomal protein S14. Tasheva, E.S., Roufa, D.J. Genes Dev. (1995) [Pubmed]
  5. Transcriptional control of metabolic regulation genes by carbohydrates. Vaulont, S., Kahn, A. FASEB J. (1994) [Pubmed]
  6. Gene expression: nutrient control of pre- and posttranscriptional events. Clarke, S.D., Abraham, S. FASEB J. (1992) [Pubmed]
  7. S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth. Martel, P.M., Bingham, C.M., McGraw, C.J., Baker, C.L., Morganelli, P.M., Meng, M.L., Armstrong, J.M., Moncur, J.T., Kinlaw, W.B. Exp. Cell Res. (2006) [Pubmed]
  8. Duplicated Spot 14 genes in the chicken: characterization and identification of polymorphisms associated with abdominal fat traits. Wang, X., Carre, W., Zhou, H., Lamont, S.J., Cogburn, L.A. Gene (2004) [Pubmed]
  9. Assignment of the "spot 14" gene (THRSP) to human chromosome band 11q13.5 by in situ hybridization. Moncur, J.T., Park, J.P., Maloney, M., Mohandas, T.K., Kinlaw, W.B. Cytogenet. Cell Genet. (1997) [Pubmed]
  10. Molecular Cloning and Expression of the Duplicated Thyroid Hormone Responsive Spot 14 (THRSP) Genes in Ducks. Zhan, K., Hou, Z.C., Li, H.F., Xu, G.Y., Zhao, R., Yang, N. Poult. Sci. (2006) [Pubmed]
  11. Spot 14 protein-protein interactions: evidence for both homo- and heterodimer formation in vivo. Cunningham, B.A., Maloney, M., Kinlaw, W.B. Endocrinology (1997) [Pubmed]
  12. Studies of the nurse cells and follicular epithelial cells during oogenesis in the diving beetle Dytiscus marginalis. Verma, G.P., Baluni, D.C. Folia morphologica. (1990) [Pubmed]
  13. Cloning, expression and regulation of the human S14 gene. Ota, Y., Mariash, A., Wagner, J.L., Mariash, C.N. Mol. Cell. Endocrinol. (1997) [Pubmed]
  14. A mouse model of resistance to thyroid hormone produced by somatic gene transfer of a mutant thyroid hormone receptor. Hayashi, Y., Mangoura, D., Refetoff, S. Mol. Endocrinol. (1996) [Pubmed]
  15. Progestins and androgens increase expression of Spot 14 in T47-D breast tumor cells. Heemers, H., Vanderhoydonc, F., Heyns, W., Verhoeven, G., Swinnen, J.V. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  16. "Spot 14" protein: a metabolic integrator in normal and neoplastic cells. Cunningham, B.A., Moncur, J.T., Huntington, J.T., Kinlaw, W.B. Thyroid (1998) [Pubmed]
  17. Functional analysis of human RPS14 null alleles. Martin-Nieto, J., Roufa, D.J. J. Cell. Sci. (1997) [Pubmed]
  18. Tissue printing and its applications in self-incompatibility studies. Cappadocia, M., Heizmann, P., Dumas, C. Plant Mol. Biol. (1993) [Pubmed]
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