Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle

Tenga, Milagros J.; Lazar, Iuliana M.

Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle

dc.contributor.author	Tenga, Milagros J.	en
dc.contributor.author	Lazar, Iuliana M.	en
dc.contributor.department	Chemistry	en
dc.date.accessioned	2014-11-25T21:20:51Z	en
dc.date.available	2014-11-25T21:20:51Z	en
dc.date.issued	2014	en
dc.description.abstract	Background: Cancer cells are characterized by a deregulated cell cycle that facilitates abnormal proliferation by allowing cells to by-pass tightly regulated molecular checkpoints such as the G1/S restriction point. To facilitate early diagnosis and the identification of new drug targets, current research efforts focus on studies that could lead to the development of protein panels that collectively can improve the effectiveness of our response to the detection of a life-threatening disease. Methods: Estrogen-responsive MCF-7 cells were cultured and arrested by serum deprivation in the G1-stage of the cell cycle, and fractionated into nuclear and cytoplasmic fractions. The protein extracts were trypsinized and analyzed by liquid chromatography - mass spectrometry (MS), and the data were interpreted with the Thermo Electron Bioworks software. Biological characterization of the data, selection of cancer markers, and identification of protein interaction networks was accomplished with a combination of bioinformatics tools provided by GoMiner, DAVID and STRING. Results: The objective of this work was to explore via MS proteomic profiling technologies and bioinformatics data mining whether randomly identified cancer markers can be associated with the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells, and whether any functional networks can be identified between these markers and placed in the broader context of cell regulatory pathways. The study enabled the identification of over 2000 proteins and 153 cancer markers, and revealed for the first time that the G1-stage of the cell cycle is not only a rich source of cancer markers, but also a host to an intricate network of functional relationships within the majority of these markers. Three major clusters of interacting proteins emerged: (a) signaling, (b) DNA repair, and (c) oxidative phosphorylation. Conclusions: The identification of cancer marker regulatory components that act not alone, but within networks, represents an invaluable resource for elucidating the moxlecular mechanisms that govern the uncontrolled proliferation of cancer cells, as well as for catalyzing the development of protein panels with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies aimed at pursuing multiple drug targets.	en
dc.description.sponsorship	This work was supported by grants from Virginia Tech and NCI (R21CA126669-01A1) to I. M. Lazar. The publication of this article was supported by Virginia Tech’s Open Access Subvention Fund.	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Tenga and Lazar: Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle. BMC Cancer 2014 14:710.	en
dc.identifier.doi	https://doi.org/10.1186/1471-2407-14-710	en
dc.identifier.uri	http://hdl.handle.net/10919/50927	en
dc.identifier.volume	14	en
dc.language.iso	en	en
dc.publisher	BioMed Central	en
dc.rights	Creative Commons Attribution 2.0 Generic	en
dc.rights.uri	http://creativecommons.org/licenses/by/2.0/	en
dc.subject	Cell cycle	en
dc.subject	Cancer markers	en
dc.subject	Proteomics	en
dc.subject	Mass spectrometry	en
dc.title	Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle	en
dc.title.serial	BMC Cancer	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en