The phosphatidylinositol 3-kinase (PI3K)/Akt pathway controls several important biological functions, such as cell growth regulation, apoptosis, and migration. However, the way in which PI3K/Akt controls androgen receptor (AR)-mediated prostate cancer cell growth remains unclear and controversial. Here Prostate cancer is the second leading cause of cancer-related death among men in the United States. The normal prostate and prostate cancers at early stages require androgen for growth and survival. In addition to androgen signaling, which plays an essential role in survival of prostate cancer, the phosphatidylinositol 3-kinase (PI3K) 1 /Akt pathway represents another important survival signal for prostate cancer cells. It appears that these two pathways can compensate for each other in growth regulation of prostate cancer LNCaP cells, because androgen treatment can rescue cells from apoptosis induced by application of PI3K inhibitors (1). Furthermore, activation of the PI3K/Akt pathway protects cells from apoptosis induced by serum starvation and androgen deprivation (2).Recent rapid progress of the PI3K/Akt signal pathway studies, as well as its influence on the androgen receptor (AR)-mediated prostate cancer growth, has resulted in many exciting yet controversial results. Here we address these controversial results by summarizing Akt-AR-related results and provide new data, as well as possible explanations for the distinct roles of the PI3K/Akt pathway in AR-mediated prostate cancer growth. Particular emphases will be: 1) Akt suppresses versus induces AR activity, 2) Akt phosphorylation sites on AR protein, and 3) promotion of AR degradation by the PI3K/Akt pathway. EXPERIMENTAL PROCEDURESReagents-pCDNA3 cAkt (3) and mutant AR S210A/S790A were described previously (4). pCDNA3-PTEN was a gift from Dr. Charles L. Sawyers, and pGEX-KG-PTEN was from Dr. Frank B. Furnari. Insulinlike growth factor-1 (IGF-1) and LY294002 was from Calbiochem. 5␣-Dihydrotestosterone (DHT), doxycycline (Dox), and cycloheximide were from Sigma. The anti-AR polyclonal antibody, NH27, was produced as described previously (3). The mouse monoclonal PTEN and prostatespecific antigen (PSA) antibodies and the goat polyclonal ␤-actin antibody were from Santa Cruz Biotechnology. The mouse monoclonal Akt and phospho-Akt (Ser 473 ) antibodies were purchased from Cell Signaling.Cell Culture and Transfections-DU145, PC-3, and COS-1 cell lines were maintained in Dulbecco's minimum essential medium containing penicillin (25 units/ml), streptomycin (25 g/ml), and 10% fetal calf serum (FCS). LNCaP cells were maintained in RPMI 1640 with 10% FCS. Transfections were performed using SuperFect TM according to standard procedures (Qiagen).Luciferase Reporter Assays-Luciferase reporter assay was as described previously with some modifications (5). The cells were transfected with plasmids in 10% charcoal-stripped serum (CSS) medium for 16 h and then treated with ethanol or 10 nM DHT for 16 h. The cells were lysed, and luciferase activity was detected by the dua...

Background The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus , a seed feeder of the family Lygaeidae. Results The 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but also to elucidate patterns of molecular evolution and physiology. We find ongoing, lineage-specific expansion and diversification of repressive C2H2 zinc finger proteins. The discovery of intron gain and turnover specific to the Hemiptera also prompted the evaluation of lineage and genome size as predictors of gene structure evolution. Furthermore, we identify enzymatic gains and losses that correlate with feeding biology, particularly for reductions associated with derived, fluid nutrition feeding. Conclusions With the milkweed bug, we now have a critical mass of sequenced species for a hemimetabolous insect order and close outgroup to the Holometabola, substantially improving the diversity of insect genomics. We thereby define commonalities among the Hemiptera and delve into how hemipteran genomes reflect distinct feeding ecologies. Given Oncopeltus ’s strength as an experimental model, these new sequence resources bolster the foundation for molecular research and highlight technical considerations for the analysis of medium-sized invertebrate genomes. Electronic supplementary material The online version of this article (10.1186/s13059-019-1660-0) contains supplementary material, which is available to authorized users.

The origin of germline cells was a crucial step in animal evolution. Therefore, in both developmental biology and evolutionary biology, the mechanisms of germline specification have been extensively studied over the past two centuries. However, in many animals, the process of germline specification remains unclear. Here, we show that in the cephalochordate amphioxus Branchiostoma floridae, the germ cell-specific molecular markers Vasa and Nanos become localized to the vegetal pole cytoplasm during oogenesis and are inherited asymmetrically by a single blastomere during cleavage. After gastrulation, this founder cell gives rise to a cluster of progeny that display typical characters of primordial germ cells (PGCs). Blastomeres separated at the two-cell stage grow into twin embryos, but one of the twins fails to develop this Vasa-positive cell population, suggesting that the vegetal pole cytoplasm is required for the formation of putative PGCs in amphioxus embryos. Contrary to the hypothesis that cephalochordates may form their PGCs by epigenesis, our data strongly support a preformation mode of germ cell specification in amphioxus. In addition to the early localization of their maternal transcripts in the putative PGCs, amphioxus Vasa and Nanos are also expressed zygotically in the tail bud, which is the posterior growth zone of amphioxus. Thus, in addition to PGC specification, amphioxus Vasa and Nanos may also function in highly proliferating somatic stem cells.

Androgens and the androgen receptor (AR) play important roles in the testes. Previously we have shown that male total AR knockout (T-AR