Photo of Arthur B. Pardee,   Ph.D.

Arthur B. Pardee, Ph.D.

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-5114
Fax: (617) 632-5739


arthur_pardee@dfci.harvard.edu

Arthur B. Pardee, Ph.D.

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Emeritus, Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • Chief, Cell Growth and Regulation, Dana-Farber Cancer Institute

Research Abstract

A major focus of research activities in this laboratory is to identify and characterize clinically useful breast cancer markers by using differential RNA-display technique. We have identified several genes by this approach and large-scale hybridization array studies have identified gene clusters whose patterns of expression in human breast tumor biopsy specimens are linked with clinical parameters including estrogen receptor status and tumor stage. Similar analysis revealed differential expression of HSIX-1, a homeobox gene in human breast cancer cells and HLM gene that shows homology with oxysterol binding protein in human lung cancers. Both of these genes showed significantly increased expression in metastatic cells. In addition, HSIX1 was shown to play a role in the DNA-damage-induced G2 cell cycle checkpoint. Our results demonstrate that HSIX1 overexpression leads to more aggressive tumors. Futhermore, a novel gene identified by differential display technique and designated as 055 is suppressed in metastatic colon cancer tissues and metastatic colon cancer cell line SW620. The working hypothesis is that overexpression of 055 gene suppresses metastasis by inducing colon cancer cell differentiation and reversing the malignant phenotype.

Another research focus of this laboratory is to identify alternative target-directed therapy for human breast cancers, more specifically for anti-hormone resistant breast cancers. This is based on targeting downstream site or sites of hormone dependent and hormone independent pathways of enhanced proliferation of breast cancer cells. An approach which is also currently investigated in this laboratory is differentiation therapy. Compounds that are found to induce terminal cellular differentiation, cell cycle arrest and apoptosis are proposed to be potential therapeutic agents for human breast cancers. One of our therapeutic studies revealed that when cancer cells, more specifically protstate cancer cells, are treated simultaneously with compounds activating more than one cell cycle check points, the conflicting regulatory signals induce apoptosis of cancer cells, thus providing a new avenue for developing anti-cancer therapy.

Publications

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  • Pardee AB. Bioregulation. J Cell Physiol 2015. PubMed
  • Li Y, Rogoff HA, Keates S, Gao Y, Murikipudi S, Mikule K, Leggett D, Li W, Pardee AB, Li CJ. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A 2015; 112:1839-44. PubMed
  • Qiao M, Shi Q, Pardee AB. The pursuit of oncotargets through understanding defective cell regulation. 2011; 1:544-51. PubMed
  • Martin KJ, Fournier MV, Reddy GP, Pardee AB. A need for basic research on fluid-based early detection biomarkers. Cancer Res 2010; 70:5203-6. PubMed
  • Qiao M, Wang Y, Xu X, Lu J, Dong Y, Tao W, Stein J, Stein GS, Iglehart JD, Shi Q, Pardee AB. Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Mol Cell 2010; 38:512-23. PubMed
  • Sheng S,Qiao M,Pardee AB. Metastasis and AKT activation. J Cell Physiol 2008; 218:451-4. PubMed
  • Qiao M,Sheng S,Pardee AB. Metastasis and AKT activation. Cell Cycle 2008; 7:2991-6. PubMed
  • Pardee AB,Qiao M. A devious cube of cancer. J Cell Physiol 2008; 216:1-2. PubMed
  • Qiao M, Pardee AB. Biomarkers, regerons, and pathways to lethal cancer. J Cell Biochem 2007; 102:1076-86. PubMed
  • Singh S, Shi Q, Bailey ST, Palczewski MJ, Pardee AB, Iglehart JD, Biswas DK. Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer. Mol Cancer Ther 2007; 6:1973-82. PubMed
  • Qiao M, Iglehart JD, Pardee AB. Metastatic potential of 21T human breast cancer cells depends on Akt/protein kinase B activation. Cancer Res 2007; 67:5293-9. PubMed
  • Liang P, Meade JD, Pardee AB. A protocol for differential display of mRNA expression using either fluorescent or radioactive labeling. Nat Protoc 2007; 2:457-70. PubMed
  • Pardee AB. Tumor progression--targets for differential therapy. J Cell Physiol 2006; 209:589-91. PubMed
  • Monks NR, Pardee AB. Targeting the NF-kappaB pathway in estrogen receptor negative MDA-MB-231 breast cancer cells using small inhibitory RNAs. J Cell Biochem 2006; 98:221-33. PubMed
  • Pardee AB. Regulatory molecular biology. Cell Cycle 2006; 5:846-52. PubMed
  • Wang A, Li CJ, Reddy PV, Pardee AB. Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation. Cancer Res 2005; 65:7809-14. PubMed
  • Geng Y, Yu Q, Whoriskey W, Dick F, Tsai KY, Ford HL, Biswas DK, Pardee AB, Amati B, Jacks T, Richardson A, Dyson N, Sicinski P. Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proc Natl Acad Sci U S A 2001; 98:13138-43. PubMed
  • Biswas DK, Dai SC, Cruz A, Weiser B, Graner E, Pardee AB. The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for estrogen receptor negative breast cancers. Proc Natl Acad Sci U S A 2001; 98:10386-91. PubMed
  • Martin KJ, Graner E, Li Y, Price LM, Kritzman BM, Fournier MV, Rhei E, Pardee AB. High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood. Proc Natl Acad Sci U S A 2001; 98:2646-51. PubMed
  • Biswas DK, Cruz A, Pettit N, Mutter GL, Pardee AB. A therapeutic target for hormone-independent estrogen receptor-positive breast cancers. Mol Med 2001; 7:59-67. PubMed
  • Martin KJ, Kritzman BM, Price LM, Koh B, Kwan CP, Zhang X, Mackay A, O'Hare MJ, Kaelin CM, Mutter GL, Pardee AB, Sager R. Linking gene expression patterns to therapeutic groups in breast cancer. Cancer Res 2000; 60:2232-8. PubMed
  • Biswas DK, Reddy PV, Pickard M, Makkad B, Pettit N, Pardee AB. Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter. J Biol Chem 1998; 273:33817-24. PubMed
  • Molnar GM, Crozat A, Kraeft SK, Dou QP, Chen LB, Pardee AB. Association of the mammalian helicase MAH with the pre-mRNA splicing complex. Proc Natl Acad Sci U S A 1997; 94:7831-6. PubMed
  • Zhang JL, Sharma PL, Li CJ, Dezube BJ, Pardee AB, Crumpacker CS. Topotecan inhibits human immunodeficiency virus type 1 infection through a topoisomerase-independent mechanism in a cell line with altered topoisomerase I. Antimicrob Agents Chemother 1997; 41:977-81. PubMed
  • Dezube BJ, Ahlers CM, Lawrence JP, Teng EI, Silberman SL, Pardee AB, Finberg RW. Tenidap inhibits replication of the human immunodeficiency virus-1 in cultured cells. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 14:13-7. PubMed
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