Imaging the Vascular and Metabolic Impact on Claudin-7, a Tight Junction Protein, in Transgenic Human Breast Cancer Models

摘要

Breast cancer is the second leading cause of cancer death in women and incidence rates continue to rise. While survival rates of women diagnosed with early stages of breast cancer have significantly improved, the survival rates of women with more advanced disease remain quite poor. Thus, novel diagnostic, prognostic, and therapeutic modalities are needed. Metastasis is the primary cause of fatality in breast cancer patients and is believed to begin with the loss of cell adhesion in neoplastic epithelium. Although tight junctions (TJs) have clearly been shown to play a role in cell adhesion, their potential role in cancer progression has been scarcely studied. In 1998, a new family of TJ proteins named Claudins (CLDNs) was discovered (1, 2), which are now known to be the main sealing proteins of the TJ. Although changes in tight junction permeability have been observed in several types of cancer, little is known about the role of CLDNs in cancer. Despite the high degree of sequence similarity among the 20 CLDN family members there is evidence suggesting that each CLDN may have a unique biological function. For example, CLDN 1-deficient mice have been shown to die within 1 day of birth despite the presence of CLDN 4, while CLDN 3 and 4 alone serve as receptors for Clostridium perfringens enterotoxin (CPE). This proposal arose out of observations that several members of the claudin gene family were differentially expressed in invasive ductal carcinomas of the breast (3). Compared to normal breast, Claudin-7 expression was lost in 50% of breast carcinomas, while Claudin 3 and 4 were generally overexpressed in breast carcinomas (3).