An Update on Cancer Cluster Activities at the Centers for Disease Control and Prevention

The Centers for Disease Control and Prevention (CDC) continues to be aware of the need for response to public concern as well as to state and local agency concern about cancer clusters. In 1990 the CDC published the “Guidelines for Investigating Clusters of Health Events,” in which a four-stage process was presented. This document has provided a framework that most state health departments have adopted, with modifications pertaining to their specific situations, available resources, and philosophy concerning disease clusters. The purpose of this present article is not to revise the CDC guidelines; they retain their original usefulness and validity. However, in the past 15 years, multiple cluster studies as well as scientific and technologic developments have affected cluster science and response (improvements in cancer registries, a federal initiative in environmental public health tracking, refinement of biomarker technology, cluster identification using geographic information systems software, and the emergence of the Internet). Thus, we offer an addendum for use with the original document. Currently, to address both the needs of state health departments as well as public concern, the CDC now a) provides a centralized, coordinated response system for cancer cluster inquiries, b) supports an electronic cancer cluster listserver, c) maintains an informative web page, and d) provides support to states, ranging from laboratory analysis to epidemiologic assistance and expertise. Response to cancer clusters is appropriate public health action, and the CDC will continue to provide assistance, facilitate communication among states, and foster the development of new approaches in cluster science

Structural Cues from the Tissue Microenvironment Are Essential Determinants of the Human Mammary Epithelial Cell Phenotype

Historically, the study of normal human breast function and breast disorders has been significantly impaired by limitations inherent to available model systems. Recent improvements in human breast epithelial cell lines and three-dimensional (3-D) culture systems have contributed to the development of in vitro model systems that recapitulate differentiated epithelial cell phenotypes with remarkable fidelity. Molecular characterization of these human breast cell models has demonstrated that normal breast epithelial cell behavior is determined in part by the precise interplay that exists between a cell and its surrounding microenvironment. Recent functional studies of integrins in a human model system provide evidence to support the idea that the structural stability afforded by integrin-mediated cell-extracellular matrix interactions is an important determinant of normal cellular behavior, and that alterations in tissue structure can give rise to tumorigenic progression

AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis