That genetic mutations contribute to cancer is undisputed. What now emerges is that a cancer cell's microenvironment has a much stronger hand in the course a cancer takes than previously thought. ©2008 Nature Publishing Group.

The transcription factor GATA-3 is necessary for the formation of a mammary gland and the maintenance of mammary-cell differentiation. The loss of GATA-3 function in a fully formed mammary gland generates oestrogen receptor-negative, proliferating cells that lack expression of myoepithelial markers. Cells with similar characteristics in breast cancer are associated with poor prognosis.

Genomic integrity is maintained by a network of cellular activities that assesses the status of the genome at a given point in time and that provides signals to proceed with or to halt cell cycle progression. Recent studies have identified cellular proteins that are the targets for the viral oncoproteins involved in these processes. We demonstrate that the expression of human papilloma virus type 16 E6 and E7 oncoproteins in normal mortal cells disrupts the integration of the network of signals that maintain genomic integrity. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc., A Wiley Company

A pivotal study reveals a long-sought-after mechanism for gene amplification and provides important implications for oncogenesis.

Individuals carrying deleterious BRCA1 mutations typically develop basal-like rather than luminal breast cancers. In this issue of Cell Stem Cell, Proia et al. (2011) study breast tissue from women with heterozygous BRCA1 mutations and identify molecular mechanisms that regulate mammary progenitor cell differentiation and bias toward subsequent basal-like tumor formation.

Adhesion-dependent cell signaling is known to be important in carcinogenesis. It is postulated that several types of adhesion molecules act as tumor suppressor genes by enforcing cell-substrate and cell-cell adhesion thereby preventing the migration of cells and their invasion into surrounding tissues. Recent evidence, however, suggests that disruption of adhesion systems can both initiate neoplastic transformation and contribute a rate-limiting step to progression. Adhesion may modulate neoplastic processes by altering pathways that control genomic stability. Analysis of the adhesion-controlled inactivation of the p53 protein and the concomitant relaxation of cell cycle checkpoint control could identify the critical contributions of adhesion-mediated influences to carcinogenesis.

The majority of studies of neoplastic transformation have focused attention on events that occur within transformed cells. These cell autonomous events result in the disruption of molecular pathways that regulate basic activities of the cells such as proliferation, death, movement and genomic integrity. Other studies have addressed the microenvironment of tumor cells and documented its importance in supporting tumor progression. Recent work has begun to expand on these initial studies of tumor microenvironment and now provide novel insights into the possible initiation and progression of malignant cells. This review will address the transforming effect of stromal cells on epithelial components.

Recently, in Nature Medicine, Schedin and colleagues define attributes within the involuting postpartum breast microenvironment that promote breast cancer metastasis. Cell invasiveness is controlled by a positive feedback loop involving COX-2 and fibrillar collagen. NSAIDs suppress tumor progression during postpartum involution, potentially providing effective agents for intervention in pregnant women.