A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission.

One of the hallmarks of cancer is hromosome stability (CIN), which leads to aneuploidy, translocations, and other chromosome aberrations. However, in the vast majority of human tumors the molecular basis of CIN remains unknown, partly because not all genes controlling chromosome transmission have yet been identified. To address this question, we developed an experimental high-throughput imaging (HTI) siRNA assay that allows the identification of novel CIN genes.

Genomic analysis of epithelial ovarian cancer.

Ovarian cancer is a major health problem for women in the United States. Despite evidence of considerable heterogeneity, most cases of ovarian cancer are treated in a similar fashion. The molecular basis for the clinicopathologic characteristics of these tumors remains poorly defined.

Differentially expressed nucleolar TGF-beta1 target (DENTT) shows tissue-specific nuclear and cytoplasmic localization and increases TGF-beta1-responsive transcription in primates.

Differentially Expressed Nucleolar TGF-beta1 Target (DENTT) is a new member of the TSPY/TSPY-like/SET/NAP-1 (TTSN) superfamily whose mRNA is induced by TGF-beta1 in TGF-beta1-responsive human lung cancer cells. Monkey DENTT mRNA contains a 2085-bp open reading frame that encodes a predicted polypeptide of 695 amino acids with five nuclear localization signals, two coiled-coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. RT-PCR amplification and Western blot analyses showed DENTT mRNA and protein in adult monkey tissues, including the adrenal gland, cerebral cortex, and ovary.

Characterization of adrenomedullin in non-human primates.

Adrenomedullin (AM) is a 52 amino acid peptide involved in the pathophysiology of several human diseases. Here we show the gene structure, organ distribution, and regulated expression of AM in monkey. The monkey AM (mAM) gene is located on the short arm of chromosome 9 and it codes for a 185 amino acid preprohormone, which contains two amidated peptides identical to the human AM and proadrenomedullin N-terminal 20 peptide.

Depressed adrenomedullin in the embryonic transforming growth factor-beta1 null mouse becomes elevated postnatally.

Transforming growth factor-beta (TGF-beta) and adrenomedullin are multifunctional regulatory proteins which are expressed in developing embryonic and adult tissues. Because of their colocalization, TGF-beta1 and adrenomedullin may be able to coordinately act to influence development and differentiation. In order to learn more about the biology of adrenomedullin in the absence of the effects of TGF-beta1 in vivo, we examined adrenomedullin in the TGF-beta1 null mouse.

Expression of differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) in adult mouse tissues.

Differentially expressed nucleolar TGF-beta1 target (DENTT) is a novel member of the TSPY/TSPY-L/SET/NAP-1 (TTSN) superfamily that we have previously identified in human lung cancer cells. Here, we have investigated the expression of this protein in the adult mouse. By Western analysis, DENTT is highly expressed in the pituitary gland and moderately in the adrenals, brain, testis, and ovary.