Eppley Institute for Research in Cancer and Allied Diseases

About: Eppley Institute for Research in Cancer and Allied Diseases is a based out in . It is known for research contribution in the topics: Pancreatic cancer & Cancer. The organization has 965 authors who have published 1396 publications receiving 58994 citations.

Deletion of Tip30 leads to rapid immortalization of murine mammary epithelial cells and ductal hyperplasia in the mammary gland

Abstract: Transformation of mammary epithelial cells (MECs) from the normal to the neoplastic stage requires the dysregulation of tumor suppressor genes and proto-oncogenes. Tip30 is a tumor suppressor that can inhibit estrogen receptor-mediated transcription in MECs, but its role in MEC proliferation remains unknown. Here, we show that deleting the Tip30 gene leads to ductal hyperplasia in mouse mammary glands early in life and extensive mammary hyperplasia with age. Tip30(-/-) mammary glands transplanted into wild-type mammary fat pads also display mammary trees with extensive ductal hyperplasia. Strikingly, Tip30 deletion promotes proliferation of primary MECs and results in rapid immortalization of MECs in vitro relative to wild-type cells. Gene array analysis identified significant increases in the expression of mammary epithelial growth factors Wisp2 and Igf-1 in Tip30(-/-) cells. Knockdown of either Wisp2 or Igf-1 using short interfering RNA dramatically inhibited proliferation of Tip30(-/-) cells. Together, these results suggest that Tip30 is an intrinsic and negative regulator of MEC proliferation partly through the inhibition of Wisp2 and Igf-1 expression, and its absence in the mammary gland may predispose MECs to neoplastic transformation.

Tool developments for structure-function studies of host defense peptides.

Abstract: Antimicrobial peptides, or host defense peptides, are universal signaling and effector molecules in host defense and innate immunity. This article highlights various tools developed for cathelicidins and defensins, ranging from peptide identification, production, and structural biology, including the eight databases for antimicrobial peptides. Novel peptides can be identified from natural sources at both gene and protein levels. Solid-phase synthesis and bacterial expression are the two important methods for peptide production. Three-dimensional structures of antimicrobial peptides, primarily de- termined by solution NMR techniques, are essential for an in-depth understanding of the mode of action. The introduction of octanoyl phosphatidylglycerol as a bacterial membrane-mimetic model provides new insights into peptide-lipid interac- tions. The incorporation of structure and activity data into the antimicrobial peptide database (http://aps.unmc.edu/AP/main.html) will lead to an integrated understanding of these peptides via structural bioinformat- ics.

Unfolding and Disassembly of the Chaperonin GroEL Occurs via a Tetradecameric Intermediate with a Folded Equatorial Domain

Abstract: The chaperonin GroEL is a homotetradecamer in which the subunits (Mr 57 000) are joined through noncovalent forces. This study reports on the unfolding and disassembly of GroEL in guanidine hydrochloride and urea. Kinetic and equilibrium measurements were made using amide hydrogen exchange/mass spectrometry, light scattering, and size-exclusion chromatography. Hydrogen exchange in GroEL destabilized in 1.8 M GdHCl (the unfolding midpoint is 1.2 M GdHCl) shows that the apical and intermediate domains unfold 3.1 times faster than the equatorial domain. Light scattering measurements made under the same conditions show that disassembly of the native GroEL tetradecamer occurs at the same rate as unfolding of the equatorial domain. This study of the kinetics of GroEL unfolding and disassembly demonstrates the existence of an intermediate that was identified as a tetradecamer with the apical and intermediate domains unfolded. Although this intermediate was easily detected in dynamic unfolding measurements, its p...