Expression of PC-cell-derived growth factor in breast cancer

  • Haiping SongEmail author
  • Lan Shi
  • Chunping Liu
  • Tao Huang
Research Article


This study is mainly aimed at evaluating the expression of PC-cell-derived growth factor (PCDGF) in breast cancer and breast adenofibroma, and to compare with other commonly used clinical pathological indices, then to investigate the diagnostic and targeted therapeutic purpose of PCDGF in breast cancer tissue. In this study, we detected the expression of PCDGF, p53 and CerbB-2 in breast cancer tissue and the expression of PCDGF in breast adenofibroma tissue by immunohistochemical method, and analyzed the relationship between them. We found that PCDGF was expressed in most breast cancer tissue, but was not in breast adenofibroma tissue, and the expression of PCDGF was related with the tumor’s pathological category and the expression of estrogen receptor (ER) and progesterone receptor (PR) and p53, but there was no statistical dependability between PCDGF and cerbB-2. From this study, we predict that PCDGF may serve as a marker in the secondary diagnosis of breast cancer, and may participate in the generation and differentiation of breast cancer cells, and become an effective target of therapy for breast cancer.


PC-cell-derived growth factor breast neoplasms clinical markers 


  1. 1.
    Hoskins K, Weber B L. The biology of breast cancer. Curr Opin Oncol, 1994, 6(6): 554–559CrossRefPubMedGoogle Scholar
  2. 2.
    Reiss K, Valentinis B, Tu X, Xu S Q, Baserga R. Molecular markers of IGF-I-mediated mitogenesis. Exp Cell Res, 1998, 242(1): 367–372CrossRefGoogle Scholar
  3. 3.
    Tangkeangsirisin W, Serrero G. PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Carcinogenesis, 2004, 25(9): 1587–1592CrossRefPubMedGoogle Scholar
  4. 4.
    Zanocco-Marani T, Bateman A, Romano G, Valentinis B, He Z H, Baserga R. Biological activities and signaling pathways of the granulin/epithelin precursor. Cancer Res, 1999, 59(20): 5331–5340PubMedGoogle Scholar
  5. 5.
    Tangkeangsirisin W, Hayashi J, Serrero G. PC cell-derived growth factor mediates tamoxifen resistance and promotes tumor growth of human breast cancer cells. Cancer Res, 2004, 64(5): 1737–1743CrossRefPubMedGoogle Scholar
  6. 6.
    Lu R Q, Serrero G. Inhibition of PC cell-derived growth factor (PCDGF, epithelinygranulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. PNAS, 2000, 97(8): 3993–3998CrossRefPubMedGoogle Scholar
  7. 7.
    Kuang S Q, Liao L, Zhang H, Lee A V, O’Malley B W, Xu J M. AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Cancer Res, 2004, 64(5): 1875–1885CrossRefPubMedGoogle Scholar
  8. 8.
    Shi L, Song H P, Liu C P, Huang T. Effect of PC-cell derived growth factor shRNA on estrogen dependent of estrogen receptor negative breast cancer cell lines. Zhonghua Wai Ke Za Zhi, 2007, 45(7): 483–486 (in Chinese).PubMedGoogle Scholar
  9. 9.
    Huang T, Song H P, Zhang J H. Effect of PCDGF shRNA on growth, proliferation, apoptosis of human breast carcinoma cell line MCF-7 and expression of VEGF. Ai Zheng, 2006, 25(3): 303–307 (in Chinese)PubMedGoogle Scholar
  10. 10.
    Bhandari V, Bateman A. Structure and chromosomal location of the human granulin gene. Biochem Biophys Res Commun, 1992, 188(1): 57–63CrossRefPubMedGoogle Scholar
  11. 11.
    Bateman A, Belcourt D, Bennett H, Lazure C, Solomon S. Granulins, a novel class of peptide from leukocytes. Biochem Biophys Res Commun, 1990, 173(3): 1161–1168CrossRefPubMedGoogle Scholar
  12. 12.
    Bhandari V, Giaid A, Bateman A. The complementary deoxyribonucleic acid sequence, tissue distribution, and cellular localiza-tion of the rat granulin precursor. Endocrinology, 1993, 133(6): 2682–2689CrossRefPubMedGoogle Scholar
  13. 13.
    Sparro G, Galdenzi G, Eleuteri A M, Angeletti M, Schroeder W, Fioretti E. Isolation and N-terminal sequence of multiple forms of granulins in human urine. Protein Expr Purif, 1997, 10(2): 169–174CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang H, Serrero G. Inhibition of the tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor). Proc Natl Acad Sci USA, 1998, 95(24): 14202–14207CrossRefPubMedGoogle Scholar
  15. 15.
    Lu R, Serrero G. Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Proc Natl Acad Sci USA, 2000, 97(8): 3993–3998CrossRefPubMedGoogle Scholar
  16. 16.
    Lu R, Serrero G. Mediation of estrogen mitogenic effect in human breast cancer MCF-7 cells by PC cell-derived growth factor (PCDGF/granulin precursor). Proc Natl Acad Sci USA, 2001, 98(1): 142–147CrossRefPubMedGoogle Scholar
  17. 17.
    Lu R, Serrero G. Stimulation of PC cell-derived growth factor (epithelin/granulin precursor) expression by estradiol in human breast cancer cells. Biochem Biophys Res Commun, 1999, 256(1): 204–207CrossRefPubMedGoogle Scholar
  18. 18.
    Moriya T, Kanomata N, Kozuka Y, Fukumoto M, Iwachido N, Hata S, Takahashi Y, Miura H, Ishida K, Watanabe M. Usefulness of immunohistochemistry for differential diagnosis between benign and malignant breast lesions. Breast Cancer, 2009, 16(3): 173–178CrossRefPubMedGoogle Scholar
  19. 19.
    Hosaka N, Ryu T, Cui W, Li Q, Nishida A, Miyake T, Takaki T, Inaba M, Ikehara S. Relationship of p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis. J Clin Pathol, 2006, 59(7): 692–698CrossRefPubMedGoogle Scholar
  20. 20.
    Liau L M, Lallone R L, Seitz R S, Buznikov A, Gregg J P, Kornblum H I, Nelson S F, Bronstein J M. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res, 2000, 60(5): 1353–1360PubMedGoogle Scholar
  21. 21.
    He Z, Bateman A. Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res, 1999, 59(13): 3222–3229PubMedGoogle Scholar
  22. 22.
    Naeem M, Nasir A, Aman Z, Ahmad T, Samad A. Frequency of HER-2/neu receptor positivity and its association with other features of breast cancer. J Ayub Med Coll Abbottabad, 2008, 20(3): 23–26PubMedGoogle Scholar
  23. 23.
    Vinothini G, Murugan R S, Nagini S. Evaluation of molecular markers in a rat model of mammary carcinogenesis. Oncol Res, 2009, 17(10): 483–493CrossRefPubMedGoogle Scholar
  24. 24.
    Carlsson J, Soussi T, Persson B. Investigation and prediction of the severity of p53 mutants using parameters from structural calculations. FEBS J, 2009, 276(15): 4142–4155CrossRefPubMedGoogle Scholar
  25. 25.
    Vinothini G, Murugan R S, Nagini S. Evaluation of molecular markers in a rat model of mammary carcinogenesis. Oncol Res, 2009, 17(10): 483–493CrossRefPubMedGoogle Scholar
  26. 26.
    Seewaldt V L, Mrók K, Sigle R, Dietze E C, Heine K, Hockenbery D M, Hobbs K B, Caldwell L E. Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix-induced apoptosis. J Cell Biol, 2001, 155(3): 471–486CrossRefPubMedGoogle Scholar
  27. 27.
    Sivaraman L, Conneely O M, Medina D, O’Malley B W. p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis. PNAS, 2001, 98(22): 12379–12384CrossRefPubMedGoogle Scholar
  28. 28.
    Shilkaitis A, Green A, Punj V, Steele V, Lubet R, Christov K. Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis by inducing cellular senescence via a p16-dependent but p53-independent mechanism. Breast Cancer Res, 2005, 7(6): R1132–R1140CrossRefPubMedGoogle Scholar
  29. 29.
    Hirsch F R, Scagliotti G V, Langer C J, Varella-Garcia M, Franklin W A. Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer, 2003, 41 Suppl 1: S29–S42CrossRefPubMedGoogle Scholar
  30. 30.
    Kim J A. Targeted therapies for the treatment of cancer, Am J Surg, 2003, 186(3): 264–268CrossRefPubMedGoogle Scholar
  31. 31.
    Murphy C G, Modi S. HER2 breast cancer therapies: a review. Biologics, 2009, 3: 289–301PubMedGoogle Scholar
  32. 32.
    Martín-Orozco R M, Almaraz-Pro C, Rodríguez-Ubreva F J, Cortés M A, Ropero S, Colomer R, López-Ruiz P, Colás B. EGF prevents the neuroendocrine differentiation of LNCaP cells induced by serum deprivation: the modulator role of PI3K/Akt. Neoplasia, 2007, 9(8): 614–624CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer Berlin Heidelberg 2009

Authors and Affiliations

  • Haiping Song
    • 1
    Email author
  • Lan Shi
    • 1
  • Chunping Liu
    • 1
  • Tao Huang
    • 1
  1. 1.Thyroid and Breast Surgical Center, Union HospitalHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations