Bone marrow stroma influences transforming growth factor-beta production in breast cancer cells to regulate c-myc activation of the preprotachykinin-I gene in breast cancer cells

Cancer Research
Hyun S OhPranela Rameshwar

Abstract

Breast cancer cells (BCCs) have preference for the bone marrow (BM). This study used an in vitro coculture of BCCs and BM stroma to represent a model of early breast cancer metastasis to the BM. The overarching hypothesis states that once BCCs are in the BM, microenvironmental factors induce changes in the expression of genes for cytokines and preprotachykinin-I (PPT-I) in both BCCs and stromal cells. Consequently, the expression of both PPT-I and cytokines are altered to facilitate BCC integration within BM stroma. Cytokine and transcription factor arrays strongly suggested that transforming growth factor-beta (TGF-beta) and c-myc regulate the expression of PPT-I so as to facilitate BCC integration among stroma. Northern analyses and TGF-beta bioassays showed that stromal cells and BCCs influence the level of PPT-I and TGF-beta in each other. In cocultures, PPT-I and TGF-beta expressions were significantly (P < 0.05) increased and decreased, respectively. TGF-beta and PPT-I were undetectable in separate stromal cultures but were expressed as cocultures. Two consensus sequences for c-myc in the 5' flanking region of the PPT-I gene were shown to be functional using gel shift and reporter gene assays. Mutagenesis of c-myc sites, ...Continue Reading

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Citations

Feb 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bobby Y ReddyPranela Rameshwar
Dec 19, 2006·Journal of Clinical Pathology·Michal NowickiBogdan Miskowiak
Jan 1, 2008·Journal of Oncology·Shyam A PatelPranela Rameshwar
Sep 7, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Christopher H ContagBonnie L King
Nov 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hiral J PatelPranela Rameshwar
Jan 16, 2014·The Indian Journal of Surgery·Anjana Nigam
Apr 12, 2007·Expert Review of Proteomics·Ruo-Pan Huang
Jan 27, 2006·Expert Opinion on Biological Therapy·Shakti H RamkissoonPranela Rameshwar
Feb 8, 2005·Biochemical and Biophysical Research Communications·Toshiyuki Yoneda, Toru Hiraga
Aug 19, 2007·Clinica Chimica Acta; International Journal of Clinical Chemistry·Katherine LiuPranela Rameshwar
Aug 30, 2008·Journal of Cellular and Molecular Medicine·Katherine LiuPranela Rameshwar
May 17, 2014·Stem Cells Translational Medicine·Sarah A BlissPranela Rameshwar
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kelly E CorcoranPranela Rameshwar

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