Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1990 Feb;9(2):407–414. doi: 10.1002/j.1460-2075.1990.tb08125.x

hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.

C Tomasetto 1, M C Rio 1, C Gautier 1, C Wolf 1, M Hareuveni 1, P Chambon 1, R Lathe 1
PMCID: PMC551681  PMID: 2303034

Abstract

Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.

Full text

PDF
409

Images in this article

408Fig. 3.
on p.408
408Fig. 3.
on p.408
409Fig. 5.
on p.409
410Fig. 7.
on p.410
410Fig. 8.
on p.410
410Fig. 9.
on p.410

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Baker M. E. Oestrogen-induced pS2 protein is similar to pancreatic spasmolytic polypeptide and the kringle domain. Biochem J. 1988 Jul 1;253(1):307–309. doi: 10.1042/bj2530307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berry M., Nunez A. M., Chambon P. Estrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1218–1222. doi: 10.1073/pnas.86.4.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown A. M., Jeltsch J. M., Roberts M., Chambon P. Activation of pS2 gene transcription is a primary response to estrogen in the human breast cancer cell line MCF-7. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6344–6348. doi: 10.1073/pnas.81.20.6344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Drenth J., Low B. W., Richardson J. S., Wright C. S. The toxin-agglutinin fold. A new group of small protein structures organized around a four-disulfide core. J Biol Chem. 1980 Apr 10;255(7):2652–2655. [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Frandsen E. K., Jørgensen K. H., Thim L. Receptor binding of pancreatic spasmolytic polypeptide (PSP) in rat intestinal mucosal cell membranes inhibits the adenylate cyclase activity. Regul Pept. 1986 Dec 30;16(3-4):291–297. doi: 10.1016/0167-0115(86)90028-5. [DOI] [PubMed] [Google Scholar]
  8. Frandsen E. K. Receptor binding of pancreatic spasmolytic polypeptide in intestinal mucosal cells and membranes. Regul Pept. 1988 Jan;20(1):45–52. doi: 10.1016/0167-0115(88)90056-0. [DOI] [PubMed] [Google Scholar]
  9. Hoefsloot L. H., Hoogeveen-Westerveld M., Kroos M. A., van Beeumen J., Reuser A. J., Oostra B. A. Primary structure and processing of lysosomal alpha-glucosidase; homology with the intestinal sucrase-isomaltase complex. EMBO J. 1988 Jun;7(6):1697–1704. doi: 10.1002/j.1460-2075.1988.tb02998.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoffmann W. A new repetitive protein from Xenopus laevis skin highly homologous to pancreatic spasmolytic polypeptide. J Biol Chem. 1988 Jun 5;263(16):7686–7690. [PubMed] [Google Scholar]
  11. Hoosein N. M., Thim L., Jørgensen K. H., Brattain M. G. Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells. FEBS Lett. 1989 Apr 24;247(2):303–306. doi: 10.1016/0014-5793(89)81357-2. [DOI] [PubMed] [Google Scholar]
  12. Hunziker W., Spiess M., Semenza G., Lodish H. F. The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein. Cell. 1986 Jul 18;46(2):227–234. doi: 10.1016/0092-8674(86)90739-7. [DOI] [PubMed] [Google Scholar]
  13. Jakowlew S. B., Breathnach R., Jeltsch J. M., Masiakowski P., Chambon P. Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7. Nucleic Acids Res. 1984 Mar 26;12(6):2861–2878. doi: 10.1093/nar/12.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jeltsch J. M., Roberts M., Schatz C., Garnier J. M., Brown A. M., Chambon P. Structure of the human oestrogen-responsive gene pS2. Nucleic Acids Res. 1987 Feb 25;15(4):1401–1414. doi: 10.1093/nar/15.4.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jørgensen K. D., Diamant B., Jørgensen K. H., Thim L. Pancreatic spasmolytic polypeptide (PSP): III. Pharmacology of a new porcine pancreatic polypeptide with spasmolytic and gastric acid secretion inhibitory effects. Regul Pept. 1982 Mar;3(3-4):231–243. doi: 10.1016/0167-0115(82)90128-8. [DOI] [PubMed] [Google Scholar]
  16. Jørgensen K. H., Thim L., Jacobsen H. E. Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas. Regul Pept. 1982 Mar;3(3-4):207–219. doi: 10.1016/0167-0115(82)90126-4. [DOI] [PubMed] [Google Scholar]
  17. Kieny M. P., Lathe R., Lecocq J. P. New versatile cloning and sequencing vectors based on bacteriophage M13. Gene. 1983 Dec;26(1):91–99. doi: 10.1016/0378-1119(83)90039-2. [DOI] [PubMed] [Google Scholar]
  18. Land H., Schütz G., Schmale H., Richter D. Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature. 1982 Jan 28;295(5847):299–303. doi: 10.1038/295299a0. [DOI] [PubMed] [Google Scholar]
  19. Lathe R. Synthetic oligonucleotide probes deduced from amino acid sequence data. Theoretical and practical considerations. J Mol Biol. 1985 May 5;183(1):1–12. doi: 10.1016/0022-2836(85)90276-1. [DOI] [PubMed] [Google Scholar]
  20. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  21. Levitt N., Briggs D., Gil A., Proudfoot N. J. Definition of an efficient synthetic poly(A) site. Genes Dev. 1989 Jul;3(7):1019–1025. doi: 10.1101/gad.3.7.1019. [DOI] [PubMed] [Google Scholar]
  22. Masiakowski P., Breathnach R., Bloch J., Gannon F., Krust A., Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982 Dec 20;10(24):7895–7903. doi: 10.1093/nar/10.24.7895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nunez A. M., Berry M., Imler J. L., Chambon P. The 5' flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein. EMBO J. 1989 Mar;8(3):823–829. doi: 10.1002/j.1460-2075.1989.tb03443.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Proudfoot N. The end of the message and beyond. Nature. 1984 Feb 2;307(5950):412–413. doi: 10.1038/307412a0. [DOI] [PubMed] [Google Scholar]
  25. Rio M. C., Bellocq J. P., Daniel J. Y., Tomasetto C., Lathe R., Chenard M. P., Batzenschlager A., Chambon P. Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa. Science. 1988 Aug 5;241(4866):705–708. doi: 10.1126/science.3041593. [DOI] [PubMed] [Google Scholar]
  26. Rio M. C., Bellocq J. P., Gairard B., Koehl C., Renaud R., Chambon P. Expression spécifique du gène humain pS2 dans les cancers du sein. Biochimie. 1988 Jul;70(7):961–968. doi: 10.1016/0300-9084(88)90238-6. [DOI] [PubMed] [Google Scholar]
  27. Rio M. C., Bellocq J. P., Gairard B., Rasmussen U. B., Krust A., Koehl C., Calderoli H., Schiff V., Renaud R., Chambon P. Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9243–9247. doi: 10.1073/pnas.84.24.9243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rio M. C., Lepage P., Diemunsch P., Roitsch C., Chambon P. Structure primaire de la protéine humaine pS2. C R Acad Sci III. 1988;307(19):825–831. [PubMed] [Google Scholar]
  29. Semenza G. Anchoring and biosynthesis of stalked brush border membrane proteins: glycosidases and peptidases of enterocytes and renal tubuli. Annu Rev Cell Biol. 1986;2:255–313. doi: 10.1146/annurev.cb.02.110186.001351. [DOI] [PubMed] [Google Scholar]
  30. Soule H. D., Vazguez J., Long A., Albert S., Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973 Nov;51(5):1409–1416. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  31. Strydom D. J. Homology of functionally diverse proteins. J Mol Evol. 1977 Aug 5;9(4):349–361. doi: 10.1007/BF01796098. [DOI] [PubMed] [Google Scholar]
  32. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thim L. A new family of growth factor-like peptides. 'Trefoil' disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins). FEBS Lett. 1989 Jun 19;250(1):85–90. doi: 10.1016/0014-5793(89)80690-8. [DOI] [PubMed] [Google Scholar]
  34. Thim L. A surprising sequence homology. Biochem J. 1988 Jul 1;253(1):309–309. doi: 10.1042/bj2530309a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Thim L., Jørgensen K. H., Jørgensen K. D. Pancreatic spasmolytic polypeptide (PSP): II. Radioimmunological determination of PSP in porcine tissues, plasma and pancreatic juice. Regul Pept. 1982 Mar;3(3-4):221–230. doi: 10.1016/0167-0115(82)90127-6. [DOI] [PubMed] [Google Scholar]
  36. Thim L., Thomsen J., Christensen M., Jørgensen K. H. The amino acid sequence of pancreatic spasmolytic polypeptide. Biochim Biophys Acta. 1985 Mar 1;827(3):410–418. doi: 10.1016/0167-4838(85)90226-2. [DOI] [PubMed] [Google Scholar]
  37. Tomasetto C., Wolf C., Rio M. C., Mehtali M., LeMeur M., Gerlinger P., Chambon P., Lathe R. Breast cancer protein PS2 synthesis in mammary gland of transgenic mice and secretion into milk. Mol Endocrinol. 1989 Oct;3(10):1579–1584. doi: 10.1210/mend-3-10-1579. [DOI] [PubMed] [Google Scholar]
  38. Wold F. In vivo chemical modification of proteins (post-translational modification). Annu Rev Biochem. 1981;50:783–814. doi: 10.1146/annurev.bi.50.070181.004031. [DOI] [PubMed] [Google Scholar]
  39. Wright C. S., Gavilanes F., Peterson D. L. Primary structure of wheat germ agglutinin isolectin 2. Peptide order deduced from X-ray structure. Biochemistry. 1984 Jan 17;23(2):280–287. doi: 10.1021/bi00297a017. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES