The life threatening characteristics of cancers lie in the uncontrolled cell mitogenic activity and the acquiring of metastatic capability. Therefore, the strategies for cancer therapy are aimed at controlling the cancer cell growth and/or inhibiting the cancer cell invasion/metastasis. Early reports contended that protein tyrosine kinase (PTK) regulatory mechanisms are clearly implicated in the growth of neoplastic cells, and inactivating specific PTKs could retard the growth of tumors. 1-3 Among the PTKs investigated, epidermal growth factor receptor (EGFR) tyrosine kinase has attracted much attention with regard to its role in transducing signal for promoting cell growth. Autophosphorylation of EGFR appears to be a potential target for cancer therapy because that would engender a blockade of the EGFR-mediated signaling. 3 In light of this, it is imperative to explore whether luteinizing hormone-releasing hormone (LHRH) analogues that possess antiproliferative activity could have any direct effects on the autophosphorylation of EGFR and its intrinsic tyrosine kinase activity.More than 3 decades have passed since the isolation and characterization of the hypothalamic LHRH, which controls the anterior pituitary secretion of luteinizing hormone and follicle stimulating hormone. 4 Accumulated data have indicated that LHRH might also present in extra-hypothalamic tissues, such as ovary, testis, kidney and placenta. 5 Currently, more than 3,000 analogues of LHRH have been synthesized. 6 Agonists of LHRH have important clinical applications in gynecology and oncology. 6 Potent antagonists of LHRH, such as Cetrorelix, are also available for clinical use. 6 The actions of LHRH and its analogues are mediated by high-affinity receptors for LHRH found on pituitary gonadotrophs and various tumors. 6 The presence of high affinity binding sites for LHRH and the expression of mRNA for LHRH receptors have been shown in human prostatic, mammary, ovarian and endometrial cancers. These LHRH receptors on tumor cells can mediate direct effects of LHRH agonists and antagonists. Inhibitory effects of LHRH agonists and antagonists on prostatic, mammary, ovarian and endometrial cancer cells have been demonstrated in vitro. 6 -11 Thus, a potent agonist ]LHRH and LHRH antagonist Cetrorelix synthesized in the laboratory of one of us (A.V.S.) 6 was shown to inhibit the growth of human ovarian endometrial and mammary cancer cells 9 and LHRH agonists Zoladex and Buserelin suppressed the proliferation of human prostate cancer lines. 7,10 The effects of LHRH-analogues on mitogenic signal transduction in cancer cells were also the subjects of extenAbbreviations: DMSO, dimethyl sulphoxide; EDTA, ethylenediamine tetraacetic acid; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ICE, interleukin-1 converting enzyme; LHRH, luteinizing hormone-releasing hormone; MMP, matrix metalloproteinase; PARP, poly(ADP-ribose) polymerase; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase; SDS-PAGE, sodium dodecyl sulphate-p...
A biochemical comparison has been made on the crystallins isolated from duck and frog lenses. Gel-permeation chromatography of lens homogenates from both classes on Fractogel TSK HW-55(S) revealed a homogeneous trimeric protein of 120 kDa in the duck lenses and a monomeric protein of 39 kDa in the frog lenses. Both crystallin fractions consist only of an approx. 3%kDa polypeptide in their subunit structures as determined by SDS gel electrophoresis. These two crystallins were compared with respect to their native molecular masses, subunit structures, peptide mapping and amino acid compositions in order to establish the identity of each crystallin. We have found differences in the protein structures of these two crystallins despite some degree of similarity in their amino acid compositions. Y-Crystallin (Frog lens, Duck lens) Amino acid composition Peptide mapping Sequence homology
Lens crystallins were isolated from the homogenate of carp (Cyprinus carpio) eye lenses by gel permeation chromatography and characterized by gel electrophoresis, immunodiffusion, amino acid analysis, circular dichroism, and protein sequence analysis. Three well-defined fractions corresponding to alpha/beta-, beta-, and gamma-crystallins were obtained in relative weight percentages of 26, 22, and 52%. The native molecular masses of the purified fractions were determined to be 410, 60, and 20 kDa, respectively. The polypeptide compositions as determined by SDS gel electrophoresis revealed the substantial presence of beta-crystallin polypeptides in the alpha-crystallin fraction; this is also evident in the fractionation of amphibian crystallins but is not common in the case of higher classes of vertebrates. The circular dichroism spectra indicate a predominant beta-sheet structure in all three fractions, albeit with some contribution of alpha-helical structure in the gamma-crystallin, the amino acid composition of which bears a resemblance to that of squid crystallin. Sequence comparison of carp gamma-crystallin with frog and calf gamma-crystallins indicates a high degree of homology in their N-terminal segments despite the dissimilarity of amino acid compositions and weak immunological cross-reactivity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.