Proteomic Study Reveals a Functional Network of Cancer Markers in the G1-Stage of the Breast Cancer Cell Cycle
Tenga, M.J.; Lazar, I.M., BMC Cancer 2014, BMC Cancer, 14, 710. DOI: 10.1186/1471-2407-14-710. EPub. Sep. 24, 2014.
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. Breast cancer is the most common cancer diagnosed in women, with ~70 % of cases displaying an estrogen receptor positive (ER+) phenotype. In the present study, mass spectrometry was used to identify proteins with biomarker utility in estrogen-responsive MCF-7 cells arrested in the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells. Over 2000 proteins and 153 cancer markers were identified. Of most relevance, the study 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. In particular, three major clusters of interacting proteins emerged: (a) cell cycle control and signaling, (b) maintenance of genome integrity and DNA repair, and (c) energy production/oxidative phosphorylation/stress and metabolism. The identification of biological regulatory components that act not alone, but within networks, represents a valuable resource for exploratory studies aimed at developing novel panels of proteins with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies that aim at pursuing multiple drug targets.
Link to publication: http://www.biomedcentral.com/1471-2407/14/710
This work was supported in part by a grant from the NCI (R21CA126669-01A1)
Tenga, M.J.; Lazar, I.M., BMC Cancer 2014, BMC Cancer, 14, 710. DOI: 10.1186/1471-2407-14-710. EPub. Sep. 24, 2014.
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. Breast cancer is the most common cancer diagnosed in women, with ~70 % of cases displaying an estrogen receptor positive (ER+) phenotype. In the present study, mass spectrometry was used to identify proteins with biomarker utility in estrogen-responsive MCF-7 cells arrested in the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells. Over 2000 proteins and 153 cancer markers were identified. Of most relevance, the study 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. In particular, three major clusters of interacting proteins emerged: (a) cell cycle control and signaling, (b) maintenance of genome integrity and DNA repair, and (c) energy production/oxidative phosphorylation/stress and metabolism. The identification of biological regulatory components that act not alone, but within networks, represents a valuable resource for exploratory studies aimed at developing novel panels of proteins with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies that aim at pursuing multiple drug targets.
Link to publication: http://www.biomedcentral.com/1471-2407/14/710
This work was supported in part by a grant from the NCI (R21CA126669-01A1)