Quantitative Organelle Proteomics of Protein Distribution in Breast Cancer MCF-7 Cells

In his address on the treatment of breast cancer, delivered in 1894 before the Harveian Society of London, W. Watson Chayne said of breast cancer: the “subject cannot be too often brought before the notice of the medical public. First, because the disease is common, at any rate in certain regions, and seems to be becoming more so”(Cheyne 1894). Although a hundred years of extensive research generated 226 946 scientific publications in the period 1886-2011, breast cancer remains the second leading cause of cancer deaths in women today. Breast cancer is the first human tumor for which targeted therapies have been developed. The most successful therapies include tamoxifen and aromatase inhibitors – both estrogen receptor pathway downregulators – and Herceptin, a HER2 antagonist that prolongs disease remission in selected women, but metastatic breast cancer remains largely an incurable disease (Imyanitov and Hanson 2004). Breast cancer shares all the hallmarks of cancer postulated by Hanahan and Weinberg (Hanahan and Weinberg 2000) that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. In addition, recent progress has added two further hallmarks such as reprogramming of energy metabolism and evading immune destruction (Hanahan and Weinberg 2011). Increasing recognition of the contribution of the tumor microenvironment to tumorigenesis re-affirms the concept of cancer as a systemic disease with very complex, not yet understood biology. In 2011 more than 7 million humans around the world will die of cancer and 465 000 women will die from breast cancer alone (Mukherjee 2011). For humanity, cancer is still the “Emperor of all maladies, master of all terrors.”(Mukherjee 2011). For scientists it remains a formidable challenge to understanding the complexity of cellular function.