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2. RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells.

Author

Shan, B., Gerez, J., Haedo, M., Fuertes, M., Theodoropoulou, M., Buchfelder, M., Losa, M., Stalla, G. K., Arzt, E., and Renner, U.

Subjects
PITUITARY tumors, CANCER cells, HYPOXIA-inducible factor 1, VASCULAR endothelial growth factors, TRANSCRIPTION factors, NEOVASCULARIZATION
Abstract

The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1α (HIF-1α). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of tumour neovascularisation. In this study, the expression and role of RSUME in pituitary tumours was studied. We found that RSUME mRNA was up-regulated in pituitary adenomas and significantly correlated with HIF-1α mRNA levels. Hypoxia (1% O2) or treatment with hypoxia-mimicking CoCl2 enhanced RSUME and HIF-1α expression, induced translocation of HIF-1α to the nuclei and stimulated VEGF-A production both in pituitary tumour cell lines and primary human pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl2-induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1α synthesis. Thus, RSUME plays an important role in initiating pituitary tumour neovascularisation through regulating HIF-1α levels and subsequent VEGF-A production and may therefore be critically involved in pituitary adenoma progression. [ABSTRACT FROM AUTHOR]

Published
2012
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3. RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells

Author

Juan Gerez, Mariana Fuertes, Günter K. Stalla, Mariana Haedo, Marco Losa, Eduardo Arzt, Bing Shan, Ulrich Renner, Michael Buchfelder, Marily Theodoropoulou, Shan, B., Gerez, J., Haedo, M., Fuertes, M., Theodoropoulou, M., Buchfelder, M., Losa, M., Stalla, G. K., Arzt, E., and Renner, U.

Subjects
Adenoma, Vascular Endothelial Growth Factor A, Cancer Research, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Transcription Factor, Endocrinology, Diabetes and Metabolism, Biology, Pituitary neoplasm, Mice, Endocrinology, Pituitary adenoma, Cell Line, Tumor, Internal medicine, Tumor Cells, Cultured, medicine, Animals, Humans, Pituitary Neoplasms, Secretion, Pituitary Neoplasm, RNA, Messenger, Hypoxia, Transcription factor, Messenger RNA, Neovascularization, Pathologic, Animal, Pituitary tumour, Cobalt, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Otras Ciencias Médicas, Vascular endothelial growth factor A, Oncology, Cell culture, Cancer research, RSUME, Transcription Factors, Human
Abstract

The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1a (HIF-1a). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of tumour neovascularisation. In this study, the expression and role of RSUME in pituitary tumours was studied. We found that RSUME mRNA was up-regulated in pituitary adenomas and significantly correlated with HIF-1a mRNA levels. Hypoxia (1% O2) or treatment with hypoxia-mimicking CoCl2 enhanced RSUME and HIF-1a expression, induced translocation of HIF-1a to the nuclei and stimulated VEGF-A production both in pituitary tumour cell lines and primary human pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl2-induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1a synthesis. Thus, RSUME plays an important role in initiating pituitary tumour neovascularisation through regulating HIF-1a levels and subsequent VEGF-A production and may therefore be critically involved in pituitary adenoma progression. Fil: Shan, B.. Max-Planck-Institut für Psychiatrie; Alemania Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Haedo, Mariana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Fuertes, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Theodoropoulou, M.. Max-Planck-Institut für Psychiatrie; Alemania Fil: Buchfelder, M.. Universitat Erlangen-Nuremberg; Alemania Fil: Losa, M.. Istituto San Raffaele; Italia Fil: Stalla, G.. Max-Planck-Institut für Psychiatrie; Alemania Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Renner, U.. Max-Planck-Institut für Psychiatrie; Alemania

Published
2012

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