Breast Cancer Research and Treatment

, Volume 71, Issue 1, pp 21–35

Involvement of breast epithelial-stromal interactions in the regulation of protein tyrosine phosphatase-γ (PTPγ) mRNA expression by estrogenically active agents

  • Suling Liu
  • Samuel K. Kulp
  • Yasuro Sugimoto
  • Jiahua Jiang
  • Hsiang-lin Chang
  • Young C. Lin
Article

Abstract

Background. Protein tyrosine phosphatase γ (PTPγ) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicate that estradiol-17β (E2)-induced suppression of PTPγ may play a role in mammary tumorigenesis. Zeranol (Z), a nonsteroidal growth promoter with estrogenic activity that is used by the US meat industry, induces estrogenic responses in primary cultured breast cells and breast cancer cell lines.

Methods. PTPγ mRNA expression in human breast tissues and cells isolated from surgical specimens of mammoplasty and breast cancer patients were detected and quantified by RT-PCR. Immunohistochemical staining was used to localize PTPγ in human breast tissues. Breast epithelial and stromal cells were isolated and co-cultured to determine the involvement of cell–cell interaction in the regulation of PTPγ mRNA expression by E2 and Z.

Results. PTPγ mRNA expression was lower in cancerous than in normal breast tissues. Both E2 and Z suppressed PTPγ mRNA levels in cultured normal breast tissues by ∼80%, but had a lesser effect in cultured epithelial cells isolated from normal breast tissues. In the co-culture system, both E2 and Z suppressed PTPγ mRNA to a greater degree in epithelial cells than in stromal cells. In whole breast tissues, PTPγ was immunolocalized to the epithelium. Treatment with E2 or Z diminished PTPγ staining indicating reductions in PTPγ at the protein level.

Conclusions. The results indicate that both E2 and Z regulate PTPγ expression in human breast and that epithelial–stromal cells interaction is important in the regulation of PTPγ expression by estrogenically active agents.

epithelial cell epithelial-stromal interaction estrogen human breast human breast cancer immunohistochemical staining protein tyrosine phosphatase γ stromal cell zeranol 

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References

  1. 1.
    Hunter T, Cooper JA: Protein tyrosine kinase. Proc Natl Acad Sci USA 77(3): 1311–1315, 1980Google Scholar
  2. 2.
    Bishop M: The search for genetics damage in neoplastic cells has become a central theme of contemporary cancer research. Trends Genet 1: 245–249, 1985Google Scholar
  3. 3.
    Ushiro H, Cohen S: Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Bill Chem 255(18): 8363–8365,1980Google Scholar
  4. 4.
    Shock LP, Bare DJ, Klinz PF, Maness PF: Protein tyrosine phosphotases expressed in developing brain and retinal Mullerglia. Mol Brain Res 28: 110–116, 1995Google Scholar
  5. 5.
    Gaits F, Li RY, Ragab A, Ragab-Thomas JMF, Chap H: Increase in receptor-like protein tyrosine phophatase activity and expression level on density-dependent growth arrest of endothelial cells. Biochem J 311: 97–103, 1995Google Scholar
  6. 6.
    LaForgia S, Morse B, Levy J, Barnea G, Cannizzaro LA, Li F, Nowell PC, Boghosian-sell L, Glick J, Weston A, Harris CC, Drabkin H, Patterson D, Crose CM, Schlessinger J, Huebner K: Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21. Proc Natl Acad Sci USA 88(11): 5036–5040, 1991Google Scholar
  7. 7.
    LaForgia S, Lasota J, Latif F, Boghosian-sell L, Kastury K, Ohta M, Druck T, Atchison L, Cannizzaro L, Barnea G, Schlessinger J, Modi W, Kuzmin I, Tory K, Zbar B, Croce CM, Lerman M, Huebner K: Detailed genetic and physical map of 3p chromosome region surrounding the familial RCC chromosome translocation, t(3;8)(p14.2;q24.1). Cancer Res 53:3118–3124, 1993Google Scholar
  8. 8.
    Lubinski J, Hadaczek P, Podolski J, Toloczko A, Sikorski A, McCue P, Druck T, Huebner K: Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas. Cancer Res 54: 3710–3713, 1994Google Scholar
  9. 9.
    Kaplan R, Morse B, Huebner K, Croce C, Ravera M, Ricca G, Jaye M, Schlessinger J: Cloning of three novel human tyrosine phosphatases reveals the existence of a multigene family of receptor-linked protein tyrosine phosphatases. Proc Natl Acad Sci USA 87: 7000–7004, 1990Google Scholar
  10. 10.
    Krueger NX, Streuli M, Saito H: Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J 9: 3241–3252, 1990Google Scholar
  11. 11.
    Stamenkovic I, Sgroi D, Aruffo A, Sy MS, Anderson T: The B lymphocyte adhesion molecule CD22 interacts with leukocyte common antigen CD45RO on T cells and α2-6 sialotransferase, CD75, on B cells. Cell 66: 1133–1144,1991Google Scholar
  12. 12.
    Zondag GCM, Koningstein GM, Jiang Y-P, Sap J, Moolwnaar WH, Gebbink MFBG: Homophilic interactions mediated by receptor tyrosine phosphatases µ κ a critical role for the novel extracellular MAM domain.J Biol Chem270: 14247–14250, 1995Google Scholar
  13. 13.
    Barnea G, Silvennoinen O, Shaanan B, Honegger AM, Canoll PD, D'Eustachio P, Morse B, Levy JB, LaForgia S, Huebner K, Musacchio JM, Sap J, Schlessinger J: Identification of a carbonic anhydrase-like domain in the extracellular region of RPTPγ defines a new subfamily of receptor tyrosine phosphatase. Mol Cell Biol 13: 1497–1506, 1993Google Scholar
  14. 14.
    Levy JB, Canoll PD, Silvennoinen O, Barnea G, Morse B, Honegger AM, Huang J-T, Cannizzaro LA, Park S-H, Druck T, Huebner K, Sap J, Ehrlich M, Musacchio JM. Schlessinger J: The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system. J Biol Chem 268: 10573–10581, 1993Google Scholar
  15. 15.
    Krueger NX, Saito H: A human transmembrane proteintyrosine phosphatase, PTP, is expressed in brain and has Nterminal receptor domain homologous to carbonic anhydrases.Proc Natl Acad Sci USA 89: 7417–7421, 1992Google Scholar
  16. 16.
    Tsukamoto T, Takahashi T, Ueda R, Hibi K, Saito H, Takahashi T: Molecular analysis of the protein-tyrosine phosphataseγ gene in human lung cancer cell lines. Cancer Res 51: 3506–3509, 1992Google Scholar
  17. 17.
    Hennipman A, van Oirschot BA, Smits J, Rijksen G, Staal GEJ: Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue. Cancer Res 49: 516–521, 1989Google Scholar
  18. 18.
    Ross JS, Fletcher JA: The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy. Semin Cancer Biol 9(2): 125–138, 1999Google Scholar
  19. 19.
    Ghoussoub RA, Dillon DA, D'Aquila T, Rimm EB, Fearon ER, Rimm DL: Expression of c-met is a strong independent prognostic factor in breast carcinoma. Cancer 82: 1513–1520, 1998Google Scholar
  20. 20.
    van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, Sakaue M, Luttrell LM, Lefkowitz RJ: Receptor tyrosine kinase and G beta gamma MAP kinase activation by a common signaling pathway.Nature 376: 781–784, 1995Google Scholar
  21. 21.
    Lin YC, Mulla Z, Kulp SK, Sugimoto Y, Farrar WB, Brueggemeier RW: Biological activity in serum and meat of Zeranolimplanted beef cattle: regulation of proliferation and estrogeninduced gene expression in normal breast cells and MCF-7 cells. Proc. 10th Int Cong Endocrinology P2-798, 1996Google Scholar
  22. 22.
    Irshaid F, Kulp SK, Sugimoto Y, Lee K, Lin YC: Zeranol stimulates estrogen-regulated gene expression on MCF-7 human breast cancer cells and normal human breast epithelial cells. Biol Reprod 60(suppl 1): 234–235, 1999Google Scholar
  23. 23.
    Lin YC, Kulp SK, Sugimoto Y, Brueggemeier RW: Potential risk of growth promoter in beef for breast cancer growth. Era of Hope, Dept. Defense Breast Cancer Res Progr Meet Proc II: 480, 2000Google Scholar
  24. 24.
    Katzenellenbogen BS, Kendra KL, Norman MJ, Berthois Y: Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res 47: 4355–4360, 1987Google Scholar
  25. 25.
    Mishra S, Hamburger AW: O-phospho-L-tyrosine inhibits cellular growth by activating protein tyrosine phosphatases. Cancer Res 53: 557–563, 1993Google Scholar
  26. 26.
    Freiss G, Vignon F: Antiestrogens increase protein tyrosine phosphatase activity in human breast cancer cells. Mol Endocrinol 8: 1389–1396, 1994Google Scholar
  27. 27.
    Lin YC, Chang CJG, Sugimoto Y, Chen R, Canatan H, Brueggemeier RW, Dayton MA: Detection of protein tyrosine phosphatase γ gene in hamster kidney. Proc Amer Assoc Cancer Res 85th Ann Meet 35: 607a (Abstract #3619), 1994Google Scholar
  28. 28.
    Kulp SK, Liu S, Sugimoto Y, Brueggemeier RW, Lin YC: Localization of protein tyrosine phosphatase γ(PTPγ) to the mammary epithelium of ACI rats. Biol Reprod 62(suppl 1): 181–182, 2000Google Scholar
  29. 29.
    Zheng J, Kulp SK, Zhang Y, Sugimoto Y, Dayton MA, Govindan MV, Brueggemeier RW, Lin YC: 17β-estradiolregulated expression of protein tyrosine phosphatase gamma gene in cultured human normal breast and breast cancer cells. Anticancer Res 20: 11–20, 2000Google Scholar
  30. 30.
    Van Roozendaal CE, Klijn JG, Van Ooijen B, Claassen C, Eggermont AM, Henzen-Logmans SC, Foekens JA: Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breat tissue sources. Int J Cancer 65: 120–125, 1996Google Scholar
  31. 31.
    Donjacour AA, Cunha GR: Stromal Regulation of Epithelial Function. Kluwer Academic Publishers, Boston, 1991, pp.335-364Google Scholar
  32. 32.
    Van Roozendaal CE, Van Ooijen B, Klijn JG, Claassen C, Eggermont AM, Henzen-Logmans SC, Foekens JA: Stromal influences on breast cancer cell growth. Br J Cancer 65: 77–81, 1992Google Scholar
  33. 33.
    Hofland LJ, Van der Burg B, Van Eijck CH, Sprij DM, Van Koetsveld PM, Lamberts SW: Role of tumor-derived fibroblasts in the growth of primary cultures of human breastcancer cells: effects of epidermal growth factor and the somatostatin analogue octreotide. Int J Cancer 60: 93–99, 1995Google Scholar
  34. 34.
    Tennant JR: Evaluation of the trypan blue technique for determination of cell viability. Transplantation 2: 685–694, 1964Google Scholar
  35. 35.
    Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P: Cloning of cDNA sequences of hormoneregulated genes from the MCF-7 human breast cancer cell lines. Nucl Acids Res 10: 7895–7903, 1982Google Scholar
  36. 36.
    Laborda J: 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucl Acids Res 19: 3998, 1991Google Scholar
  37. 37.
    van Niekerk CC, Poels LG: Reduced expression of protein tyrosine phosphatase gamma in lung and ovarian tumors. Cancer Lett 137: 61–73, 1999Google Scholar
  38. 38.
    Clark R, Dickson RB, Lippman ME: Hormonal aspects of breast cancer. Growth factors, drugs and stromal interactions. Crit Rev Oncol Hematol 12: 1–23, 1992Google Scholar
  39. 39.
    Dong-LeBourhis X, Berthois Y, Millot G, Degeorges A, Sylv M, Martin P, Calvo F: Effect of stromal and epithelial cells derived from normal and tumorous breast tissue on the proliferation of human breast cancer cell lines in co-culture. Int J Cancer 71: 42–48, 1997Google Scholar
  40. 40.
    Hu Y-F: Human breast cancer and DES-inducible hamster kidney tumor: cellular and molecular analysis of hormonal carcinogenesis and chemoprevention. PhD Dissertation, The Ohio State University, 1995, pp. 76–108Google Scholar
  41. 41.
    Zhang Y: Cell-cell interactions and gossypol's effects on cell functions of primary cultured human breast epithelial, stromal and adipose stromal cells. PhD Dissertation, The Ohio State University. 1999, pp 1–34Google Scholar
  42. 42.
    Aaronson SA, Bottaro DP, Miki T, Ron D, Finch PW, Fleming TP, Ahn J, Taylor WG, Rubin JS: Keratinocyte growth factor, a fibroblast growth factor family member with unusual target cell specificity. Ann NY Acad Sci 638: 62–77, 1991Google Scholar
  43. 43.
    Cullen KJ, Lippman ME: Stromal-epithelial interactions in breast cancer. In: Dickson RB, Lippman ME (eds) Gene, Oncogenes, and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer. Kluwer Academic Publisher, Boston, 1991, pp 413–431Google Scholar
  44. 44.
    Cunha GR: Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer (suppl) 74: 1030–1044, 1994Google Scholar
  45. 45.
    Schumann G, Fiebich BL, Menzel D, Hull M, Butcher R, Nielsen P, Bauer J: Cytokine-induced transcription of proteintyrosine-phosphatases in human astrocytoma cells. Mol Brain Res 62: 56–64, 1998Google Scholar
  46. 46.
    Code of Federal Regulations. Title 21, Sections 522 and 556, U.S. Government Printing Office, Washington DC 199, p. 224 and 452Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Suling Liu
    • 1
  • Samuel K. Kulp
    • 1
  • Yasuro Sugimoto
    • 1
    • 2
  • Jiahua Jiang
    • 1
  • Hsiang-lin Chang
    • 1
  • Young C. Lin
    • 1
    • 2
  1. 1.Laboratory of Reproductive and Molecular EndocrinologyCollege of Veterinary MedicineUSA
  2. 2.The Ohio State University Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA

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