Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion.

Malignant pleural mesothelioma (MPM) is a rare and deadly malignancy with an extremely poor prognosis. The median overall survival (OS) of this disease is 12-18 months. However, the oncogenic driver mutations of MPM are rarely understood, and the targeted therapy for it is still under investigation.

Fine mapping and candidate gene analysis of qhkw5-3, a major QTL for kernel weight in maize.

KEY MESSAGE: qhkw5-3, a major QTL for kernel weight in maize, was mapped to an interval of 125.3 kb between the InDel markers InYM20 and InYM36, and the candidate genes were analysed. Yield, of which kernel weight is a major component, is the primary trait of interest in maize breeding programmes.

Enrichment of putative prostate cancer stem cells after androgen deprivation: upregulation of pluripotency transactivators concurs with resistance to androgen deprivation in LNCaP cell lines.

Background: Prostate cancer stem cells (PCSC) offer theoretical explanations to many clinical and biological behaviors of the disease in human. In contrast to approaches of using side populations and cell-surface markers to isolate and characterize the putative PCSC, we hypothesize that androgen deprivation leads to functional enrichment of putative PCSC.

Methods And Results: Human prostate cancer lines LNCaP, LAPC4 and LAPC9 were depleted of androgen in cell cultures and in castrated SCID mice.

Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model.

The translational landscape of mTOR signalling steers cancer initiation and metastasis.

The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion.

Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth.

Alteration of the PTEN/PI3K pathway is associated with late-stage and castrate-resistant prostate cancer (CRPC). However, how PTEN loss is involved in CRPC development is not clear. Here, we show that castration-resistant growth is an intrinsic property of Pten null prostate cancer (CaP) cells, independent of cancer development stage.

Anchorage-independent growth of prostate cancer stem cells.

Prostate cancer is a major health concern in the Western world. Prostate cancer stem cells have been implicated to be involved in, if not solely responsible for prostate cancer initiation and relapse after surgical, hormonal, and chemotherapy. Until now, the identity of the presumed prostate cancer stem cell has been illusive and the efforts to characterize such cells have been hampered by the lack of efficient prostate stem cell activity assay.

Simultaneous haploinsufficiency of Pten and Trp53 tumor suppressor genes accelerates tumorigenesis in a mouse model of prostate cancer.

Tumor suppressor gene PTEN is important in the initiation and progression of human prostate carcinoma, whereas the role of TP53 remains controversial. Since Pten/Trp53 double conditional knockout mice show earlier onset and fast progression of prostate cancer when compared to Pten knockout mice, we asked whether heterozygosity of these two tumor suppressor genes was sufficient to accelerate prostatic tumorigenesis. To answer this question we examined prostatic lesion progression of Pten/Trp53 double heterozygous mice and a series of controls such as Pten heterozygous, Pten conditional knockout, Trp53 heterozygous and Trp53 knockout mice.

A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression.

Transgenic expression of activated AKT1 in the murine prostate induces prostatic intraepithelial neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence. Genetic ablation of p27(Kip1) led to downregulation of senescence markers and progression to cancer.

Murine cell lines derived from Pten null prostate cancer show the critical role of PTEN in hormone refractory prostate cancer development.

PTEN mutations are among the most frequent genetic alterations found in human prostate cancers. Our previous works suggest that although precancerous lesions were found in Pten heterozygous mice, cancer progression and metastasis only happened when both alleles of Pten were deleted. To understand the molecular mechanisms underlying the role of PTEN in prostate cancer control, we generated two pairs of isogenic, androgen receptor (AR)-positive prostate epithelial lines from intact conditional Pten knock-out mice that are either heterozygous (PTEN-P2 and -P8) or homozygous (PTEN-CaP2 and PTEN-CaP8) for Pten deletion.

Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgens.

Background: Relaxin is a potent peptide hormone normally secreted by the prostate. This study characterized relaxin expression during prostate cancer progression to androgen independence (AI), and in response to androgens.

Methods: The prostate cancer cell line, LNCaP, was assayed by microarrays and confirmatory Northern analysis to assess changes in relaxin levels due to androgen treatment and in LNCaP xenografts following castration.

NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss.

We demonstrate that PTEN loss causes reduced NKX3.1 expression in both murine and human prostate cancers. Restoration of Nkx3.

Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation.

PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal cell proliferation without blocking differentiation.

Increased expression of osteopontin contributes to the progression of prostate cancer.

Osteopontin is a secreted glycosylated phosphoprotein known to be involved in numerous physiologic functions and associated with the late stages of various cancers. We used preneoplastic and neoplastic mouse models of prostate cancer to determine the onset of elevated expression of osteopontin in the development of this disease. Osteopontin alterations occurred early in the disease with dysregulated expression observed in lesions of low-grade prostatic intraepithelial neoplasia (PIN).

PTENless means more.

Recent studies indicate that certain key molecules that are vital for various developmental processes, such as Wnt, Shh, and Notch, cause cancer when dysregulated. PTEN, a tumor suppressor that antagonizes the PI3 kinase pathway, is the newest one on the list. The biological function of PTEN is evolutionarily conserved from C.

Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer.

The murine Pten prostate cancer model described in this study recapitulates the disease progression seen in humans: initiation of prostate cancer with prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma, and subsequent metastasis with defined kinetics. Furthermore, while Pten null prostate cancers regress after androgen ablation, they are capable of proliferating in the absence of androgen. Global assessment of molecular changes caused by homozygous Pten deletion identified key genes known to be relevant to human prostate cancer, including those "signature" genes associated with human cancer metastasis.

Analysis of triptolide-regulated gene expression in Jurkat cells by complementary DNA microarray.

Aim: To investigate the global gene expression profile changes in Jurkat cells after triptolide treatment in order to find the possible triptolide targets.

Methods: Jurkat cells were treated with or without triptolide 10 microg/L for 2 h. Total RNA were isolated and used as templates for reverse transcriptional labeling of fluorescent cDNA probes.

Isolation and characterization of human and mouse WDR19,a novel WD-repeat protein exhibiting androgen-regulated expression in prostate epithelium.

Androgens regulate important processes involved in the normal development and function of the human and rodent prostate glands. Here we report the isolation and characterization of a new androgen-regulated gene, designated WDR19, that encodes repeating sequence motifs found in the WD-repeat family of proteins. The WD repeat is a conserved domain of approximately 40 amino acids that is typically bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides.