Our research interest is to delineate the molecular basis of early neoplastic transformation of human mammary epithelial cells. We have developed several models of breast epithelial cell immortalization. The major ongoing projects : i) isolation, immortalization and characterization of stem/progenitor cells that differentiate into different cell types of the mammary gland and represent precursors for different subtypes of breast cancers. Deliberate oncogenic transformation of different progenitor cells leads to differential oncogenic response and varying ability to differentiate ii) We have identified a novel coactivator ADA3 (alteration deficiency in activation) that regulates cell cycle by its functioning as coactivator and recruiting histone acetyl transferases to various promoters of transcription factors that are known to play important role in cell cycle; and iii) We have identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. We have recently shown that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ and infiltrating ductal carcinoma of the breast. Ecd expression levels showed a positive correlation with higher grade, mitotic index, and Nottingham Prognostic Index score. More importantly, Ecd expression was positively associated with HER2/neu overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival and disease-free survival in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.
Recent Research Highlights
- We have demonstrated a novel role of mammalian Ecdysoneless in cell cycle regulation.
- We have demonstrated that Ecdysoneless is overexpressed in breast cancers and overexpression of Ecdysoneless serves as a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.
- We have generated the first telomerase-immortalized human mammary stem/progenitor cells that maintain their ability to self renew and differentiate.
- We have demonstrated that ectopically-expressed oncogenes induce block in lineage specific differentiation of immortal human mammary stem / progenitor cells.
Vimla Band – Professor and Chair
Aditya Bele – Graduate Student
Divya Bhagirath – Graduate Student
Fnu Gayatri – Post Doc
Bryan Katafiasz – Research Technologist
Riyaz Mir – Post Doc
Sameer Mirza – Post Doc
Shakur Mohibi – Graduate Student
Shashank Srivastava – Graduate Student
June Wang - Instructor
Xiangshan Zhao – Assistant Professor
Taylor Ziegler - INBRE summer student
Lab Publications ( PubMed )
- Zhao X, Mirza S, Alshareeda A, Zhang Y, Gurumurthy CB, Bele A, Kim JH, Mohibi S, Goswami M, Lele S, West W, Qiu F, Ellis IO, Green AR, Band H, Band V. Overexpression of a novel cell cycle regulator Ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients. Breast Cancer Res and Treatment, In Press 2012. Jan 22
- Zhao X, Malhotra GK, Band H, Band V. A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes. J Carcinog. 2011;10:39. Epub 2011 Dec 31.
- Zhao X, Malhotra GK, Lele SM, Lele MS, West WW, Eudy JD, Band H and Band V. Telomerase-immortalized human mammary stem/progenitor cells with ability to self renew and differentiate. Proc. Natl. Acad. Sci. USA., 2010 107:14146-14151.
- Kim JH, Gurumurthy CB, Band H and Band V. Biochemical characterization of human Ecdysoneless reveals a role in transcriptional regulation. Biol. Chem. 2010 391:9-19.
- Kim JH, Gurumurthy CB, Naramura M, Zhang Y, Dudley AT, Doglio L, Band H, Band V. Role of mammalian Ecdysoneless in cell cycle regulation. J Biol Chem. 2009Sep 25;284(39):26402-10.
- Zhao X, Lu L, Pokhriyal N, Ma H, Duan L, Lin S, Jafari N, Band H and Band V. Overexpression of RhoA induces preneoplastic transformation of primary mammary epithelial cells. Cancer Res., 2009.Jan 15;69(2):483-91.
- Zhao X, Goswami M, Pokhriyal N, Ma H, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H, and Band V. Cyclooxygenase-2 expression during immortalization and breast cancer progression. Cancer Res., 2008, 68:467-475.
- Germaniuk-kurowska A, Nag A, Zhao X, Dimri M, Band H and Band V. Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent breast cancer cell proliferation. Cancer Res., 2007, 67:11789-11797.
- Zhao Y, Katzman RB, Delmolino L, Bhat I, Zhang Y, Gurumurthy CB, Reddi HV, Solomon A, Zeng M, Kung A, Ma H, Gao Q, Dimri G, Stanculescu A, Miele L, Wu l, Griffin JD, Wazer DE, Band H and Band V. The Notch regulator MAML1 interacts with p53 and functions as a coactivator. J. Biol. Chem. 2007;282:11969-11981.
- Nag A., Sassack M, Germaniuk-Kurowska A, Band H and Band V. Essential role of human ADA3 in p53 acetylation. J. Biol. Chem., 2007, 282:8812-8820.
Centers & Core Facilities
Bioinformatics and Systems Biology Core
- DNA Sequencing
- Electron Microscopy
Experimental Irradiation Facility
Mouse Genome Engineering Core
- Starting a Project
- Bioinformatics and Systems Biology Core
Advanced Anatomy Laboratory
- Research Labs