The Oestrogen-Regulated pS2-BCEI Protein in Breast Cancer

  • Edwin Milgrom
Conference paper
Part of the ESO Monographs book series (ESO MONOGRAPHS)


About one-third of patients with advanced breast cancer respond to hormone therapy [1]. Adequate prescription of this treatment is, therefore, required to devise means of predicting their response. Oestrogen receptor determinations have proved to be effective in this respect: receptor-negative patients displayed remission in less than 5–10% of cases, whereas remission was observed in ∼50% of ER-positive patients. In order to improve this prediction, a search was made for efficient markers of oestrogen action. One of these is the oestrogen-inducible progesterone receptor: ER+ PR+ patients have ∼75% probability to respond to hormone therapy. Also other oestrogen-responsive markers have been defined, for example, Cathepsin D [2]. Random cloning of oestrogen-responsive messenger RNAs was performed independently by 2 groups [3–5]. It allowed to define a messenger RNA called pS2 or BCEI (Breast Cancer Oestrogen Induced), which has been extensively characterised. It was studied not only as a means of predicting response to hormone therapy in advanced breast cancer, but also as a predictor of outcome in early cancer and as a model of oestrogen regulation of a human target gene.


Breast Cancer Human Breast Cancer Cell Advanced Breast Cancer Normal Breast Tissue Human Breast Cancer Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Santen RJ, Manni A, Harvey H and Redmond C: Endocrine treatment of breast cancer in women. Endocr Rev 1990 (11):221–265PubMedCrossRefGoogle Scholar
  2. 2.
    Rochefort H: Cathepsin D in breast cancer. Breast Cancer Res Treat 1990 (16):1–13CrossRefGoogle Scholar
  3. 3.
    Prud’homme JF, Fridlansky F, Le Cunff M, Atger M, Mercier Bodart C, Pichon MF and Milgrom E: Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells. DNA 1985 (4):11–21PubMedCrossRefGoogle Scholar
  4. 4.
    Jakowlew SB, Breathnach R, Jeltsch JM, Masiakowski P and Chambon P: Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF7. Nucl Acid Res 1984 (12):2861–2878CrossRefGoogle Scholar
  5. 5.
    Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A and Chambon P: Cloning of cDNA sequences of hormone regulated genes from the MCF7 human breast cancer cell line. Nucl Acid Res 1982 (10):7895–7901CrossRefGoogle Scholar
  6. 6.
    May FEB and Westley BR: Identification and characterization of estrogen regulated RNAs in human breast cancer cells. J Biol Chem 1988 (263):12901–12908PubMedGoogle Scholar
  7. 7.
    Rio MC, Lepage P, Diemunsch P, Roitsch C and Chambon P: Structure primaire de la proteine humaine pS2. CR Acad Sci III Paris 1988 (307):825–831Google Scholar
  8. 8.
    Mori K, Fujii R, Kida N, Ohta M and Hayashi K: Identification of a polypeptide secreted by human breast cancer cells (MCF7) as the human estrogen responsive gene (pS2) product. Biochem Biophys Res Commun 1988 (155):366–372PubMedCrossRefGoogle Scholar
  9. 9.
    Baker EM: Oestrogen induced pS2 protein is similar to pancreatic spasmolytic polypeptide and the kringle domain. Biochem J 1988 (253):307–311PubMedGoogle Scholar
  10. 10.
    Jorgensen KH, Thim L and Jacobsen HE: Pancreatic spasmolytic polypeptide (PSP): Preparation and initial chemical characterization of a new polypeptide from porcine pancreas. Regul Pept 1982(3):207–219PubMedCrossRefGoogle Scholar
  11. 11.
    Jorgensen KD, Diamant B, Jorgensen KH and Thim L: Pancreatic spasmolytic polypeptide (PSP): Pharmacology of a new porcine pancreatic polypeptide with spasmolytic and gastric acid secretion inhibitory effects. Regul Pept 1982 (3):231–243PubMedCrossRefGoogle Scholar
  12. 12.
    Hoosein NM, Thim L, Jorgensen KH and Brattain MG: Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells. FEBS Lett 1989 (247):303–306PubMedCrossRefGoogle Scholar
  13. 13.
    Frandsen EK, Jorgensen KH and Thim L: Receptor binding of pancreatic spasmolytic polypeptide (PSP) in rat intestinal mucosal cell membranes inhibits the adenylate cyclase activity. Regul Pept 1986 (16):291–297PubMedCrossRefGoogle Scholar
  14. 14.
    Tomasetto C, Rio MC, Gautier C, Wolf C, Hareuveni M, Chambon P and Lathe R: hSP, the domain duplicated homolog pf pS2 protein, is co expressed with pS2 in stomach but not in breast carcinoma. Embo J 1990(9):407–414PubMedGoogle Scholar
  15. 15.
    Weaver CA, Springer PA and Katzenellenbogen BS: Regulation of pS2 gene expression by affinity labeling and reversibly binding estrogens and antiestrogens: comparison of effects on the native gene and on pS2 chloramphenicol acetyltransferase fusion genes transfected into MCF7 human breast cancer cells. Mol Endocrinol 1988 (2):936–945PubMedCrossRefGoogle Scholar
  16. 16.
    May FEB and Westley BR: Effects of tamoxifen and 4 hydroxytamoxifen on the pNR 1 and pNR 2 estrogen regulated RNAs in human breast cancer cells. J Biol Chem 1987 (262):15894–15899PubMedGoogle Scholar
  17. 17.
    Westley BR, Holzel F and May FEB: Effects of oestrogen and the antioestrogens, tamoxifen and LY117018, on four oestrogen regulated RNAs in the EFM-19 breast cancer cell line. J Steroid Biochem 1989 (32):365–372PubMedCrossRefGoogle Scholar
  18. 18.
    Kida N, Yoshimura T, Mori K and Hayashi K: Hormonal regulation of synthesis and secretion of pS2 protein relevant to growth of human breast cancer cells MCF7. Cancer Res 1989 (49):3494–3498PubMedGoogle Scholar
  19. 19.
    Henry JA, Nicholson S, Hennessy, Lennard TWJ, May FEB and Westley BR: Expression of the oestrogen regulated pNR2 mRNA in human breast cancer: relation to oestrogen receptor mRNA levels and response to tamoxifen therapy. Br J Cancer 1989(61):32–38CrossRefGoogle Scholar
  20. 20.
    Pilat MJ, Hafner M and Brooks SC: Differential induction of pS2 and Cathepsin D mRNAs by structurally altered estrogens. The Endocrine Society 1991 p270Google Scholar
  21. 21.
    Davidson NE, Bronzert DA, Chambon P Gelmann EP and Lippman ME: Use of two MCF7 cell variants to evaluate the growth regulatory potential of estrogen induced products. Cancer Res 1986 (46):1904–1908PubMedGoogle Scholar
  22. 22.
    Westley B, May FEB, Brown AMC, Krust A, Chambon P, Lippman ME and Rochefort H: Effects of antiestrogens on the estrogen-regulated pS2 RNA and the 52- and 160-kilodalton proteins in MCF-7 cells and two tamoxifen-resistant sublines. J Biol Chem 1984 (259): 10030–10035PubMedGoogle Scholar
  23. 23.
    Aitken SC, Lippman ME, Kasid A and Schoenberg DR: Relationship between the expression of estrogen regulated genes and estrogen stimulated proliferation of MCF7 mammary tumor cells. Cancer Res 1985(45):2608–2615PubMedGoogle Scholar
  24. 24.
    Cavailles V, Garcia M and Rochefort H: Regulation of cathepsin D and pS2 gene expression by growth factors in MCF7 human breast cancer cells. Mol Endocrinol 1989 (3):552–558PubMedCrossRefGoogle Scholar
  25. 25.
    Brown AMC, Jeltsch JM, Roberts M and 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 USA 1984 pp 6344–6348Google Scholar
  26. 26.
    Roberts M, Wallace J, Jeltsch JM and Berry M: The 5’ flanking region of the human pS2 gene mediates its transcriptional activation by estrogen in MCF7 cells. Biochem Biophys Res Commun 1988 (151):306–313PubMedCrossRefGoogle Scholar
  27. 27.
    Berry M, Nunez AM and Chambon P: Estrogen responsive element of the human pS2 gene is an imperfectly palindromic sequence. Proc Natl Acad Sci USA 1986 pp 1218–1222Google Scholar
  28. 28.
    Nunez AM, Berry M, Imler JL and Chambon P: The 5’ flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumor promoter (TPA), 38 the c-Ha-ras oncoprotein and thec-jun protein. Embo J 1989(8):823–829.PubMedGoogle Scholar
  29. 29.
    Tomasetto C, Wolf C, Rio MC, Mehtali M, LeMeur M, Gerlinger P, Chambon P and Lathe R: Breast cancer protein pS2 synthesis in mammary gland of transgenic mice and secretion into milk. Mol Endocrinol 1989 (3):1579–1584PubMedCrossRefGoogle Scholar
  30. 30.
    Cohen Haguenauer O, Nguyen Van Cong, Prud’homme JF, Jegou-Joubert C, Gross MS, De Tand MF, Milgrom E and Frézal J: A gene expressed in human breast cancer and regulated by estrogen in MCF7 cells is located on chromosome 21. Eighth International Workshop on Human Gene Mapping 1985 (40) p 606Google Scholar
  31. 31.
    Rio MC, Bellocq JP, Gairard B, Koehl C, Renaud R and Chambon P: Expression spécifique du gene humain pS2 dans les cancers du sein. Biochimie 1988 (70):961–968PubMedCrossRefGoogle Scholar
  32. 32.
    Rio MC and Chambon P: The pS2 gene, mRNA, and protein: a potential marker for the human breast cancer. Cancer Cells 1990 (2):269–274PubMedGoogle Scholar
  33. 33.
    Prédine J, Spyratos F, Prud’homme JF, Andrieu C, Hacene K, Brunet M, Pallud C and Milgrom E: Enzyme linked immunosorbent assay (ELISA) of pS2 in breast cancers, benign tumors and normal breast tissues. Correlation with prognosis and adjuvant hormonotherapy. Cancer (in press)Google Scholar
  34. 34.
    Pallud C, Le Doussal V, Pichon MF, Prud’homme JF, Hacene K and Milgrom E: Immunohistochemistry of pS2 in normal human breast cancer and in various histological forms of breast tumors. Submitted for publicationGoogle Scholar
  35. 35.
    May FEB and Westley BR: Cloning of estrogen regulated messenger RNA sequences from human breast cancer cells. Cancer Res 1986 (46):6034–6040PubMedGoogle Scholar
  36. 36.
    Rio MC, Bellocq JP, Daniel JY, Tomasetto C, Lathe R, Chenard MP, Batzenschaler A and Chambon P: Breast cancer associated pS2 protein: synthesis and secretion by normal stomach mucosa. Science 1988 (241):705–708PubMedCrossRefGoogle Scholar
  37. 37.
    Luqmani Y, Bennett C, Paterson I, Corbishley CM, Rio MC, Chambon P and Ryall G: Expression of the pS2 gene in normal, benign and neoplastic human stomach. Int J Cancer 1989 (44):806–812PubMedCrossRefGoogle Scholar
  38. 38.
    Wysocki S, Hahnel E, Masters A, Smith V, McCartney AJ and Hahnel R: Detection of pS2 messenger RNA in gynecological cancers. Cancer Res 1990 (50):1800–1802PubMedGoogle Scholar
  39. 39.
    Takahashi H, Kida N, Fujii R, Tanaka K, Ohta M, Mori K and Hayashi K: Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma. FEBS Lett 1990 (261):283–286PubMedCrossRefGoogle Scholar
  40. 40.
    Zaretsky JZ, Weiss M, Tsarfaty I, Hareuveni M, Wreschner DH and Keydar I: Expression of genes coding for pS2, c-erbB2, estrogen receptor and the H23 breast tumor associated antigen. FEBS Lett 1990(265):46–50PubMedCrossRefGoogle Scholar
  41. 41.
    Rio MC, Bellocq JP, Gairard B, Rasmussen UB, Krust A, Koehl C, Calderoli H, Schiff V, Renaud R and 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 USA 1987 (84):9243–9247PubMedCrossRefGoogle Scholar
  42. 42.
    Foekens JA, Rio MC, Seguin P, Van Putten WLJ, Fauque J, Nap M, Klijn JGM and Chambon P: Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res 1990 (50):3832–3837PubMedGoogle Scholar
  43. 43.
    Piggott NH, Henry JA, May FEB and Westley BR: Antipeptide antibodies against the pNR-2 oestrogen regulated protein of human breast cancer cells and detection of pNR-2 expression in normal tissues by immunohistochemistry. J Pathology 1991 (163):95–104CrossRefGoogle Scholar
  44. 44.
    Prud’homme JF, Jolivet A, Pichon MF, Savouret JF and Milgrom E: Monoclonal antibodies against native and denatured forms of estrogen induced breast cancer protein (BCEI/pS2) obtained by expression in Escherichia coli. Cancer Res 1990 (50):2390–2396PubMedGoogle Scholar
  45. 45.
    Schwartz LH, Koerner FC, Edgerton SM, Sawicka JM, Rio MC, Bellocq JP, Chambon P and Thor AD: pS2 expression and response to hormonal therapy in patients with advanced breast cancer. Cancer Res 1991 (51):624–628PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • Edwin Milgrom
    • 1
  1. 1.Unité INSERM U. 135Hôpital de BicêtreLe Kremlin BicêtreFrance

Personalised recommendations