American Association for Cancer Research

May 1 Cancer Research Highlights

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Selected Articles from the May 1, 2006 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 May 1 issue of Cancer Research.


Rare Medullary Breast Cancer Gene Profile Differentiated from Ductal Breast Cancer

Bertucci et al.
Page 4636
Medullary breast cancer (MBC) is a rare but enigmatic form of breast cancer. Using whole-genome microarrays, Bertucci et al. profiled samples from 66 patients, including 22 with MBC and 44 with grade III ductal breast cancer (DBC). Most MBCs displayed a basal subtype profile. Supervised analysis identified a gene expression signature that discriminated basal MBCs from basal DBCs. Genes overexpressed in MBCs are associated with various cellular processes, including immune reaction, antigen processing, and apoptosis. Several are located in the 12p13 chromosomal region. Genes underexpressed are associated with smooth muscle cell differentiation (e.g. SMA), cytoskeleton, and cell adhesion.

 


Mouse Models Light Up Prostate Cancer Investigations

Lyons et al.
Page 4701

CAN 05-01-06 Lyons 4701Genetically engineered mouse models of prostate cancer have proven invaluable for furthering our understanding of the human disease. To facilitate their application towards preclinical drug development, Lyons et al. report several transgenic lines that enable non-invasive in vivo measurement of the murine prostate via bioluminescence imaging (BLI). One line develops spontaneous and bioluminescent prostate tumors that allow real-time visualization of primary tumor growth as well as response to intervention— even in the absence of androgen. The other line does not develop tumors, but its bioluminescent phenotype indicates that similar preclinical studies will now be possible with other transgenic models of prostate carcinoma.


Mouse Model Depicts Roles of Telomeres, p53 in Hepatocellular Carcinoma

Farazi et al.
Page 4766

Inactivation of the p53 tumor suppressor, high levels of chromosomal instability, and disease conditions causing chronic cycles of hepatocyte death and regeneration are commonly associated with human hepatocellular carcinoma. To explore the roles of these factors in hepatocarcinogenesis, Farazi et al. designed a chronic liver disease mouse model of hepatocellular carcinoma establishing cooperative interactions between telomere dysfunction and p53 mutation in the pathogenesis of this common human cancer. As this mouse model is driven by mechanisms underlying human hepatocellular carcinoma development, it may prove useful in the identification of genomic changes and serum biomarkers associated with hepatocellular carcinoma progression.


Menin Function in Histone Methylation, Transcriptional Activation Defined

Dreijerink et al.

Page 4929

CAN 05-01-06 Dreijerink 4929The menin protein is encoded by the tumor suppressor gene involved in multiple endocrine neoplasia type 1 (MEN1). Menin was found in MLL/MLL2 histone methyltransferase complexes but its molecular function remained unclear. Dreijerink et al. investigated involvement of menin in endocrine processes and found that the protein acts as an adaptor to link nuclear receptor function to trimethylation of lysine 4 of histone H3. This modification is linked with transcriptional activation. Indeed, estrogen-dependent transcription is compromised by menin knockdown. These results show promise for detailed understanding of menin function and of the molecular pathology of MEN1-associated tumorigenesis.


T Cell, Dendritic Cell Responses Suggest Vaccine Adjuvant Role for IFN-α

Di Pucchio et al.

Page 4943

The use of IFN-α in clinical oncology has mainly been based on the rationale of exploiting the antiproliferative activities of this cytokine rather than its effects on immune cells. Di Pucchio et al. performed a pilot trial to determine the effects of IFN-α, administered as adjuvant of Melan-A/MART-1 and gp100 peptides, on immune responses in melanoma patients. They observed a marked enhancement of CD8+ T cells that recognized melanoma peptides along with an increase in the percentage of monocyte/dendritic cell precursors expressing costimulatory molecules. The results represent a starting point for considering a new clinical use of IFN-α as a vaccine adjuvant.