DF/HCC Program Affiliation

Translational Pharmacology and Early Therapeutic Trials
Breast Cancer

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

• Liang P, Meade JD, Pardee AB.A protocol for differential display of mRNA expression using either fluorescent or radioactive labeling.Nat Protoc 2007;2(3):457-70.
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• 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 May 1;98(1):221-33.
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• 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 Dec 11;273(50):33817-24.
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