Breast Cancer Research and Treatment

, Volume 68, Issue 1, pp 65–73

Expression of pp32 gene family members in breast cancer

  • ShriHari S. Kadkol
  • Gamal Abou El Naga
  • Jonathan R. Brody
  • Jining Bai
  • Yuri Gusev
  • William C. Dooley
  • Gary R. Pasternack
Conference Report

Abstract

The pp32 gene family consists of at least three closely related members, pp32, pp32r1 and pp32r2. In spite of a high degree of identity at the nucleotide level, pp32 functionally behaves as a tumor suppressor where as pp32r1 and pp32r2 are pro-oncogenic. The purpose of this pilot study was to determine pp32-related expression and whether alternative gene use among the pp32 family members occurred in human breast cancer. As a first step, in situ hybridization with a riboprobe capable of hybridizing with all the three members showed abundant pp32-related mRNA in benign ducts and acini and in infiltrating ductal carcinomas. A total of 100/102 cases were positive. Further, a detailed molecular analysis by RT-PCR, cloning, and sequencing was performed in five frozen infiltrating breast carcinomas and matched benign breast tissues. Oncogenic pp32r1 (5/5) and pp32r2 (3/5) expression was observed in carcinomas where as benign breast tissues expressed pp32. 4/5 carcinomas continued to express pp32 but one was devoid of pp32 expression. These results suggest that alternative expression of pp32 family members may be common in human breast cancer and the analysis of the profile of pp32-related expression might be helpful in understanding the role of these genes in breast cancer pathogenesis.

pp32 gene expression breast cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics. CA-A Cancer J Clinic. 49: 8-31, 1999Google Scholar
  2. 2.
    Walker RA, Jones JL, Chappell S, Walsh T, Shaw JA: Molecular pathology of breast cancer and its application to clinical management. Cancer Metast Rev 16: 5-27, 1997Google Scholar
  3. 3.
    Slamon DJ, Clark G, Wong SG, Levin WJ, Ullrich A,M cGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182, 1987Google Scholar
  4. 4.
    Hubbard AL, Doris CP, Thompson AM, Chetty U, Anderson TJ: Critical determination of the frequency of c-erbB2 amplification in breast cancer. Br J Cancer 70: 434-439, 1994Google Scholar
  5. 5.
    Klijn JGM, Berns PMJJ, Schmitz PIM, Foekens JA: The clinical significance of epidermal growth factor receptor in breast cancer: a review of 5232 patients. Endocr Rev 13: 3-17, 1992Google Scholar
  6. 6.
    Osborne RJ, Merlo GR, Mitsudomi T, Venesio T, Liscia DS, Cappa APM, Chiba I, Takahashi T, Nau MM, Callahan R, Minna J: Mutations in the p53 gene in primary human breast cancers. Cancer Res 51: 6194-6198, 1991Google Scholar
  7. 7.
    Walker RA, Dearing SJ, Lane DP, Varley JM: Expression of p53 protein in infiltrating and in situ breast carcinomas. J Pathol 165: 203-211, 1991Google Scholar
  8. 8.
    Casey G: The BRCA1 and BRCA2 breast cancer genes. Curr Opin Oncol 9: 88-93, 1997Google Scholar
  9. 9.
    Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W: A strong candidate for the breast and ovarian cancer suceptibility gene BRCA1. Science 266: 66-71, 1994Google Scholar
  10. 10.
    Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G: Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789-792, 1995Google Scholar
  11. 11.
    Kadkol SS, Brody JR, Pevsner J, Bai J, Pasternack GR. Modulation of oncogenic potential by alternative gene use in human prostate cancer: Nature Med 5: 275-279, 1999Google Scholar
  12. 12.
    Fink TM, Vaesen M, Kratzin HD, Lichter P, Zimmer M: Localization of the gene encoding the putative human HLA class II-associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization. Genomics 29: 309-310, 1995Google Scholar
  13. 13.
    Walensky LD, Coffey DS, Chen TH, Wu TC, Pasternack GR: A novel M(r) 32,000 nuclear phosphoprote in is selectively expressed in cells competent for self-renewal. Cancer Res 53: 4720-4726, 1993Google Scholar
  14. 14.
    Chen TH, Brody JR, Romantsev FE, Yu JG, Kayler AE, Voneiff E, Kuhajda FP, Pasternack GR: Structure of pp32, an acidic nuclear prote in which inhibits oncogene-induced formation of transformed foci. Mol Biol Cell 7: 2045-2056, 1996Google Scholar
  15. 15.
    Brody JR, Kadkol SS, Mahmoud MM, Rebel JMJ, Pasternack GR: Identification of sequences required for inhibition of oncogene mediated transformation by pp32. J Biol Chem 274: 2005 3-20055, 1999Google Scholar
  16. 16.
    Kadkol SS, Brody JR, Epstein JI, Kuhajda FP, Pasternack GR: Novel nuclear phosphoprotein pp32 is highly expressed in intermediate-and high-grade prostate cancer. The Prostate 34: 231-237, 1998Google Scholar
  17. 17.
    Virshup DM: Protein phosphatase 2A: a panoply of enzymes. Curr Opin Cell Biol 12: 180-185, 2000Google Scholar
  18. 18.
    Yan Y, Mumby MC: Distinct roles for PP1 and PP2A in phosphorylation of the retinoblastoma protein. PP2A regulates the activities of G(1) cyclin-dependent kinases. J Biol Chem 274: 31917-31924, 1999Google Scholar
  19. 19.
    Li M, Makkinje A, Damuni Z: Molecular identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Biochemistry 35: 6998-7002, 1996Google Scholar
  20. 20.
    Bai J, Brody JR, Kadkol SS, Pasternack GR: Tumor suppression and potentiation by manipulation of pp32 expression. Oncogene 2001 (in press)Google Scholar
  21. 21.
    Brennan CM, Gallouzi IE, Steitz JA: Protein ligands to HuR modulate its interaction with target mRNAs in vivo. J Cell Biol 151: 1-14, 2000Google Scholar
  22. 22.
    Seo S-B, McMamara P, Heo S, Turner A, Lane WS, Chakravarti D: Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the Set oncoprotein. Cell 104: 119-130, 2001Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • ShriHari S. Kadkol
    • 1
  • Gamal Abou El Naga
    • 1
    • 2
  • Jonathan R. Brody
    • 1
  • Jining Bai
    • 1
  • Yuri Gusev
    • 3
  • William C. Dooley
    • 3
  • Gary R. Pasternack
    • 1
  1. 1.Division of Molecular Pathology, Department of PathologyThe Johns Hopkins University School of MedicineBaltimore
  2. 2.Department of PathologyAin Shams University School of MedicineCairoEgypt
  3. 3.Department of SurgeryThe Johns Hopkins University School of MedicineBaltimore

Personalised recommendations