Downregulation of hnRNP A2/B1 expression in tumor cells under prolonged hypoxia.

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.