TGFβ-blockade uncovers stromal plasticity in tumors by revealing the existence of a subset of interferon-licensed fibroblasts.

Despite the increasing interest in targeting stromal elements of the tumor microenvironment, we still face tremendous challenges in developing adequate therapeutics to modify the tumor stromal landscape. A major obstacle to this is our poor understanding of the phenotypic and functional heterogeneity of stromal cells in tumors. Herein, we perform an unbiased interrogation of tumor mesenchymal cells, delineating the co-existence of distinct subsets of cancer-associated fibroblasts (CAFs) in the microenvironment of murine carcinomas, each endowed with unique phenotypic features and functions.

ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.

The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761.

Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies.

A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond to drugs directed against HER2, they frequently become resistant and resume their malignant progression. Gene amplification in double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested to facilitate the acquisition of resistance to therapies targeting RTKs.

Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis.

Bmi-1 and Mel-18 are structural homologues that belong to the Polycomb group of transcriptional regulators and are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. While a number of clinical and experimental observations have implicated Bmi-1 in human tumorigenesis, the role of Mel-18 in cancer cell growth has not been investigated. We report here that short hairpin RNA-mediated knockdown of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival, anchorage-independent growth, and suppression of tumor formation in nude mice.

Insulin-like growth factor-binding protein 3 expression increases during immortalization of cervical keratinocytes by human papillomavirus type 16 E6 and E7 proteins.

Human papillomaviruses (HPVs) infect cervical epithelial cells and induce both benign and precancerous lesions. High-risk HPVs promote the development of cervical cancer in vivo and can immortalize cervical epithelial cells in vitro, whereas low-risk HPVs cannot. We used cDNA microarrays and quantitative polymerase chain reaction to compare cellular gene expression in primary cervical epithelial cells during a time course after retroviral transduction with either low-risk or high-risk E6/E7 genes.

Measurements of human papillomavirus transcripts by real time quantitative reverse transcription-polymerase chain reaction in samples collected for cervical cancer screening.

Specific assays capable of distinguishing normal and atypical cervical changes from pre-cancerous lesions are direly needed to improve screening for cervical cancer. Specific genes transcripts that are up-regulated in dysplastic and cancer cells can be exploited as new markers for cervical cancer screening provided that they can be detected in heterogeneous populations such as those collected for Papanicolaou tests. We hypothesized that expression of the HPV early region gene E7 might distinguish between normal samples (absent expression) and high-grade lesions (detectable E7 expression).