This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garayoa, M. Articles by Mulshine, J. L. Search for Related Content PubMed PubMed Citation Articles by Garayoa, M. Articles by Mulshine, J. L.

Downregulation of hnRNP A2/B1 Expression in Tumor Cells under Prolonged Hypoxia

Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Histology and Pathology, Carcinogenesis Unit, University of Navarra, Pamplona, Spain; and Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington DC.

Address correspondence to: Dr. James L. Mulshine, Intervention Section, Cell and Cancer Biology Branch, CCR, NCI, NIH, Bldg. 10, Room 12N226, 9000 Rockville Pike, Bethesda, MD 20892-1906. E-mail: mulshinj{at}mail.nih.gov

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been previously shown to be overexpressed in breast and lung tumors. Because hypoxia is a feature inherent in solid tumors, the regulation of hnRNP A2/B1 expression and subcellular localization under hypoxic conditions was studied on human lung and breast carcinoma cell lines. We found that sustained hypoxic treatment downregulated hnRNP A2/B1 expression in MCF7 and H157 cell lines. Northern blot analysis showed that this decay: (i) was observed as a marked diminution of transcript levels after 24–48 h of exposure to low oxygen tension; (ii) is not mediated by the transcription factor, hypoxia inducible factor-1; and (iii) is partially dependent on a higher hnRNP A2/B1 messenger RNA turnover under hypoxic than normoxic conditions. Immunocytochemical staining also showed a significant diminution of hnRNP A2/B1 staining in these cell lines after 24–48 h of hypoxia, together with a predominant loss of cytoplasmic staining. Further investigations are warranted to evaluate the relevance of modulation of hnRNP A2/B1 in hypoxic environments relative to its previously reported utility as a marker of early lung carcinogenesis.

Abbreviations: adenosine uridine, AU • deoxycytosinetriphosphate, dCTP • deformed epidermal autoregulatory factor-1, DEAF-1 • hypoxia-inducible factor 1, HIF-1 • heterogeneous nuclear ribonucleoprotein, hnRNP • messenger RNA, mRNA • 3' untranslated region, 3'UTR