July 1 Cancer Research Highlights

Epithelial ovarian cancer is the most common and lethal gynecologic malignancy and there have been only small improvements in survival rates over the past three decades. Kikuchi and colleagues identify a homozygous loss of angiopoietin-like protein 2 (ANGPTL2), encoding a secreted protein belonging to the angiopoietin family, in ovarian cancer cell lines. Patients showing reduced ANGPTL2 immunoreactivity had significantly worse survival in the earlier stages (stage I/II), but better survival in the advanced stages (stage III/IV). The restoration of ANGPTL2 expression or treatment with conditioned medium containing ANGPTL2 inhibited the growth of ovarian cancer cells lacking its expression, suggesting that epigenetic silencing of ANGPTL2 leads to a loss of ANGPTL2 function, which may be a factor in ovarian carcinogenesis in a stage-dependent manner.

 

Maspin is a key prostate tumor suppressor with diverse biological functions. Shao and colleagues identify a novel property of maspin in prostate development and carcinogenesis. Using maspin heterozygous mice and prostate cell lines, the authors demonstrate that loss of one copy of the gene leads to the development of epithelial hyperplastic lesions and that this effect is mediated through decreased levels of the cyclin-dependent kinase inhibitors p21 and p27. These mice also exhibited stromal hyperplasia and defective interaction between epithelial cells and basement membrane in the prostate. These findings demonstrate that maspin plays an essential role in early prostate development and in the inhibition of prostate hyperplastic lesions.

Approximately 50% of patients receiving chemotherapy do not benefit due to intrinsic or acquired multidrug resistance. Recent evidence shows that the different breast cancer subtypes (luminal, HER2⁺, and basal-like) display differential response to chemotherapy. Analyzing a panel of breast cancer cell lines using high-density single nucleotide polymorphism arrays to detect genome-wide DNA copy number changes, O’Brien and colleagues report that amplification of a region of chromosome 17 (17q21) is strongly associated with in vitro resistance to the taxane and auristatin classes of chemotherapeutics. Specifically, they identify the amplification and overexpression of the ABCC3 gene as most likely responsible for conferring resistance to these drugs. This amplicon was also present in primary breast tumors, occurring primarily in HER2⁺ tumors. They also report on the development of a specific fluorescence in situ hybridization assay that may be used as a biomarker of taxane response in breast cancer.