Publications [#174147] of G. Allan Johnson

Papers Published

1. BM Markaverich, RR Gregory, MA Alejandro, JH Clark, GA Johnson, BS Middleditch, Methyl p-hydroxyphenyllactate. An inhibitor of cell growth and proliferation and an endogenous ligand for nuclear type-II binding sites., The Journal of biological chemistry, vol. 263 no. 15 (May, 1988), pp. 7203-10, ISSN 0021-9258
   (last updated on 2010/04/30)

   Abstract:
   We previously described and partially characterized endogenous ligands for nuclear type II sites in normal and malignant tissues. Chromatography of these ligands on Sephadex LH-20 revealed that two peaks with binding activity (alpha and beta) could be resolved. The beta-peak component was present in all normal tissues that we examined, but not in malignant tissues, and it inhibited the growth of MCF-7 human breast cancer cells in vitro. Conversely, the alpha-peak component was found to be present in both normal and malignant tissues, and did not inhibit MCF-7 cell growth. The present studies describe the purification and identification of the alpha-peak and beta-peak components in bovine serum and an assessment of the effects of these compounds on normal and malignant cell growth. Gas chromatography-mass spectroscopy analysis of the purified beta-peak component demonstrated that the compound was methyl p-hydroxyphenyllactate (MeHPLA). Competition analysis revealed that MeHPLA binds to nuclear type II sites with a high binding affinity, while physiological levels of this compound blocked estradiol stimulation of uterine growth in vivo and inhibited the growth of MCF-7 human breast cancer cells in vitro. The alpha-peak component was found to be the corresponding acid, p-hydroxyphenyllactic acid (HPLA). This compound interacted with nuclear type II sites with a relatively low affinity and did not block uterotropic response to estradiol or inhibit MCF-7 cell growth. These studies demonstrate that HPLA and MeHPLA are ligands for nuclear type II sites and that MeHPLA may be a very important regulator of normal and malignant cell growth.

   Keywords:
   Animals • Breast Neoplasms • Cell Division • Cell Line • Cell Nucleus • Chromatography, Gel • Chromatography, High Pressure Liquid • Female • Humans • Lactates • Mass Spectrometry • Ovariectomy • Rats • Rats, Inbred Strains • Receptors, Estradiol • Receptors, Estrogen • drug effects* • isolation & purification • metabolism • metabolism* • pharmacology*