Alternative splicing of parathyroid hormone-related protein mRNA: Expression and stability

R. S. Sellers, A. I. Luchin, V. Richard, R. M. Brena, D. Lima, Thomas J. Rosol

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Abstract

Parathyroid hormone-related protein (PTHrP) is a multifunctional protein that is often dysregulated in cancer. The human PTHrP gene is alternatively spliced into three isoforms, each with a unique 3′-untranslated region (3′-UTR), encoding 139, 173 and 141 amino acid proteins. The regulation of PTHrP mRNA isoform expression has not been completely elucidated, but it may be affected by transforming growth factor-β1 (TGF-β1). In this study, we examined differences in the PTHrP mRNA isoform expression in two squamous carcinoma cell lines (SCC2/88 and HARA), an immortalized keratinocyte cell line (HaCaT), and spontaneous human lung cancer with adjacent normal tissue. In addition, the effect of TGF-β1 on PTHrP mRNA isoform expression and stability was examined. Cell-type specific expression of PTHrP mRNA isoforms occurred between the various cell lines, normal human lung, and immortalized human keratinocytes (HaCaT). PTHrP isoform expression pattern was significantly altered between normal lung tissue and the adjacent lung cancer. In vitro studies revealed that TGF-β1 differentially altered the mRNA steady-state levels and mRNA stability of the PTHrP isoforms. Protein-RNA binding studies identified different proteins binding to the 3′-UTR of the PTHrP isoforms (139) and (141), which may be important in the differential mRNA stability and response to cytokines between the PTHrP isoforms. The data demonstrate that there is cell-type specific expression of PTHrP mRNA isoforms, and disruption of the normal regulation during cancer progression may in part be associated with TGF-β1-induced changes in PTHrP mRNA isoform expression and stability.

Original languageEnglish (US)
Pages (from-to)227-241
Number of pages15
JournalJournal of Molecular Endocrinology
Volume33
Issue number1
DOIs
Publication statusPublished - Aug 1 2004

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Sellers, R. S., Luchin, A. I., Richard, V., Brena, R. M., Lima, D., & Rosol, T. J. (2004). Alternative splicing of parathyroid hormone-related protein mRNA: Expression and stability. Journal of Molecular Endocrinology, 33(1), 227-241. https://doi.org/10.1677/jme.0.0330227