Journal ArticleDOI
Gene expression profiling in the mammary gland of rats treated with 7,12-dimethylbenz[a]anthracene.
Andriana D. Papaconstantinou,Ilanchezhian Shanmugam,Liang Shan,Insa S. Schroeder,Cunping Qiu,Minshu Yu,Elizabeth G. Snyderwine +6 more
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TLDR
Genes regulating microtubule function, including stathmin, Ran, α‐tubulin and hsp27, were all overexpressed in the mammary gland of DMBA‐treated rats, raising the possibility that disruption of microtubules dynamics and abnormal mitosis may be critical events preceding breast cancer development.Abstract:
Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real-time PCR, RT-PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β-casein and transferrin and higher expression of hsp27 in glands from DMBA-treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki-67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α-tubulin and hsp27, were all overexpressed in the mammary gland of DMBA-treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley-Liss, Inc.read more
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Microtubule-associated proteins as targets in cancer chemotherapy.
TL;DR: It is proposed that rational microtubule-targeting cancer therapeutic approaches should ideally include proteomic profiling of tumor MAPs before administration of micro Tubule-stabilizing/destabilizing agents preferentially in combination with agents that modulate the expression of relevant MAPs.
Journal ArticleDOI
Stathmin: a protein with many tasks. New biomarker and potential target in cancer
TL;DR: Recent evidences support a role for stathmin in the regulation of cell growth and motility, both in vitro and in vivo, and indicate its involvement in advanced, invasive and metastatic cancer more than in primary tumors.
Journal ArticleDOI
A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis
Jennifer J. Schlezinger,Donghui Liu,Marganit Farago,David C. Seldin,Karine Belguise,Gail E. Sonenshein,David H. Sherr +6 more
TL;DR: A working model is proposed that may help explain the sometimes contradictory outcomes observed after AhR manipulation and that serves as a blueprint for the design of therapeutics which target the AhR in breast cancer.
Journal ArticleDOI
Fetal origins of breast cancer
TL;DR: Maternal diet and environmental exposure might increase the risk of breast cancer by inducing permanent epigenetic changes in the fetus that alter the susceptibility to factors that can initiate breast cancer.
Journal ArticleDOI
Tumor Cell Dependence on Ran-GTP–Directed Mitosis
TL;DR: It is shown that the small GTPase Ran, a regulator of mitotic spindle formation, is differentially overexpressed in human cancer as compared with normal tissues, in vivo.
References
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The STATs of cancer — new molecular targets come of age
Hua Yu,Richard Jove +1 more
TL;DR: Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance, and STAT proteins — especially STAT3 and STAT5 — regulate all of these processes and are persistence activated in a surprisingly large number of human cancers.
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Charles M. Perou,Stefanie S. Jeffrey,Matt van de Rijn,Christian A. Rees,Michael B. Eisen,Douglas T. Ross,Alexander Pergamenschikov,Cheryl F. Williams,Shirley Zhu,Jeffrey C. Lee,Deval A. Lashkari,Dari Shalon,Patrick O. Brown,David Botstein +13 more
TL;DR: The results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.
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Mammary Hyperplasia and Carcinoma in MMTV-cyclin D1 Transgenic Mice
Timothy C. Wang,Robert D. Cardiff,Lawrence R. Zukerberg,Emma Lees,Andrew Arnold,Emmett V. Schmidt +5 more
TL;DR: It is concluded that overexpression of cyclin Dl deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclIn Dl indeed plays an important oncogenic role in breast cancer.
Journal ArticleDOI
Mechanisms of Taxol resistance related to microtubules.
TL;DR: This review focuses on mechanisms of Taxol resistance that occur directly at the microtubule, such as mutations, tubulin isotype selection and post-translational modifications, and also at the level of regulatory proteins.
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Identification of a Protein That Interacts with Tubulin Dimers and Increases the Catastrophe Rate of Microtubules
TL;DR: Using a polymerization inhibition assay, a small, heat stable protein that physically interacts with tubulin dimers and increases the catastrophe rate of microtubules is purified and identified as oncoprotein 18 (Op18)/stathmin, a conserved phosphoprotein that is highly expressed in leukemia cells.