November 1 Cancer Research Highlights

Selected Articles from the November 1, 2008 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the November 1 issue of Cancer Research.

ERRα Is Critical in Growth of ER-Negative Breast Cancer

Stein et al.

Page 8805

Expression of estrogen-related receptor a (ERRα) has recently been shown to carry negative prognostic significance in breast cancer, though the specific role of this orphan nuclear receptor in tumor growth and progression is not fully understood. The sequence homology between the classical estrogen receptors (ERs) and ERRα initially suggested that these receptors were functionally similar. However, using a microarray approach, Stein and colleagues determined that most ERRα-regulated genes are unrelated to estrogen signaling. Therefore, ERRα function was evaluated in ERα-negative breast cancer cells. In this context, ERRα knockdown significantly reduced tumor growth when cells were propagated as murine xenografts. These results highlight ERRα as a potential therapeutic target in ER-negative breast cancer.

HPV Acquisition and Clearance

Goodman et al.

Page 8813

Goodman and colleagues report on a multiethnic longitudinal study in Hawaii to evaluate viral and nonviral determinants of cervical human papillomavirus (HPV) acquisition and clearance. The incidence of oncogenic HPV types decreased with age, but increased with coexisting HPV infections, suggesting a biological interaction between viral types. Other cofactors for HPV acquisition included use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Clearance times were slower for oncogenic HPV types than for nononcogenic types. These results suggest the possibility of a biological interaction between HPV types on the acquisition of cervical infection that may have implications for the effectiveness of HPV vaccines.

Endocrine Resistance in Lobular Carcinoma

Riggins et al.

Page 8908

Mechanisms of antiestrogen resistance are often studied in models of invasive ductal carcinoma; however, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancer and its incidence continues to rise. Riggins and colleagues report on a novel model of acquired tamoxifen resistance in ILC and show that up-regulation of the orphan nuclear receptor estrogen-related receptor γ (ERRγ) occurs during the acquisition of resistance, and that overexpression of ERRγ confers tamoxifen resistance to invasive lobular breast cancer cells. The authors also demonstrate that increased AP1 activity drives the resistant phenotype, the first evidence of a functional consequence for ERRγ-mediated AP1 transcription. These results provide important new insights into the mechanisms of antiestrogen resistance in invasive lobular breast carcinomas.

Common Familial Colorectal Cancer Linked to 7q31

Neklason et al.
Page 8993

Present investigations suggest that approximately 30% of colorectal cancer (CRC) cases arise on the basis of inherited factors; however, known inherited colon cancer syndromes account for <5% of colorectal cancer. Using the affected sibling-pair approach to identify genetic regions that are coinherited by siblings with CRC, Neklason and colleagues identified a major locus on chromosome 7q31.31 with a logarithm of the odds score of 3.08 (P = 0.00008). No known familial cancer genes reside in the 7q31 locus, thus the identified region may contain a novel susceptibility gene responsible for common familial CRC.

Pancreatic Tumor Neural Tropism and CX3CR1

Marchesi et al.

Page 9060
Marchesi et al.

Tumor perineural invasion occurs in diverse human malignancies but with higher frequency in pancreatic ductal adenocarcinoma (PDAC). Tumor cells harbored in nerve fibers and ganglia are a major source of tumor relapse after surgery, in spite of complete resection, and chemokines and their receptors have been implicated in this process. Marchesi and colleagues show that the chemokine receptor CX3CR1 is highly expressed in cells isolated from PDAC patients and is significantly associated with tumor perineural infiltration. The authors also show that CX3CR1 mediates chemotactic migration toward CX3CL1, the only known ligand for CX3CR1 and one of the most highly expressed chemokines in the nervous system, and that adhesive interaction with neural cells is dependent on CX3CL1. These results suggest that the CX3CR1-CX3CL1 axis could represent a valuable therapeutic target against tumor perineural dissemination in pancreatic cancer.

November 1 Cancer Research Highlights

Selected Articles from the November 1, 2008 Issue

ERRα Is Critical in Growth of ER-Negative Breast Cancer

HPV Acquisition and Clearance

Endocrine Resistance in Lobular Carcinoma

Common Familial Colorectal Cancer Linked to 7q31

Pancreatic Tumor Neural Tropism and CX3CR1

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