Genomic characterization of human and rat prolactinomas

Yunguang Tong, Yun Zheng, Jin Zhou, Nelson M. Oyesiku, H. Phillip Koeffler, Shlomo Melmed

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Although prolactinomas can be effectively treated with dopamine agonists, about 20% of patients develop dopamine resistance or tumor recurrence after surgery, indicating a need for better understanding of underlying disease mechanisms. Although estrogen-induced rat prolactinomas have been widely used to investigate the development of this tumor, the extent that the model recapitulates features of human prolactinomas is unclear. To prioritize candidate genes and gene sets regulating human and rat prolactinomas, microarray results derived from human prolactinomas and pituitaries of estrogen-treated ACI rats were integrated and analyzed. A total of 4545 differentially expressed pituitary genes were identified in estrogen-treated ACI rats [false discovery rate (FDR) <0.01]. By comparing pituitary microarray results derived from estrogen-treated Brown Norway rats (a strain not sensitive to estrogen), 4073 genes were shown specific to estrogen-treated ACI rats. Human prolactinomas exhibited 1177 differentially expressed genes (FDR < 0.05). Combining microarray data derived from human prolactinoma and pituitaries of estrogen-treated ACI rat, 145 concordantly expressed genes, including E2F1, Myc, Igf1, and CEBPD, were identified. Gene set enrichment analysis revealed that 278 curated pathways and 59 gene sets of transcription factors were enriched (FDR < 25%) in estrogen-treated ACI rats, suggesting a critical role for Myc, E2F1, CEBPD, and Sp1 in this rat prolactinoma. Similarly increased Myc, E2F1, and Sp1 expression was validated using real-time PCR and Western blot in estrogen-treated Fischer rat pituitary glands. In summary, characterization of individual genes and gene sets in human and in estrogen-induced rat prolactinomas validates the model and provides insights into genomic changes associated with this commonly encountered pituitary tumor.

Original languageEnglish (US)
Pages (from-to)3679-3691
Number of pages13
JournalEndocrinology
Volume153
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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Prolactinoma
Estrogens
Inbred ACI Rats
Genes
Dopamine Agonists
Inbred F344 Rats
Genetic Association Studies
Pituitary Neoplasms
Pituitary Gland
Real-Time Polymerase Chain Reaction
Dopamine
Neoplasms
Transcription Factors
Western Blotting

ASJC Scopus subject areas

  • Endocrinology

Cite this

Tong, Y., Zheng, Y., Zhou, J., Oyesiku, N. M., Koeffler, H. P., & Melmed, S. (2012). Genomic characterization of human and rat prolactinomas. Endocrinology, 153(8), 3679-3691. https://doi.org/10.1210/en.2012-1056

Genomic characterization of human and rat prolactinomas. / Tong, Yunguang; Zheng, Yun; Zhou, Jin; Oyesiku, Nelson M.; Koeffler, H. Phillip; Melmed, Shlomo.

In: Endocrinology, Vol. 153, No. 8, 01.08.2012, p. 3679-3691.

Research output: Contribution to journalArticle

Tong, Y, Zheng, Y, Zhou, J, Oyesiku, NM, Koeffler, HP & Melmed, S 2012, 'Genomic characterization of human and rat prolactinomas', Endocrinology, vol. 153, no. 8, pp. 3679-3691. https://doi.org/10.1210/en.2012-1056
Tong Y, Zheng Y, Zhou J, Oyesiku NM, Koeffler HP, Melmed S. Genomic characterization of human and rat prolactinomas. Endocrinology. 2012 Aug 1;153(8):3679-3691. https://doi.org/10.1210/en.2012-1056
Tong, Yunguang ; Zheng, Yun ; Zhou, Jin ; Oyesiku, Nelson M. ; Koeffler, H. Phillip ; Melmed, Shlomo. / Genomic characterization of human and rat prolactinomas. In: Endocrinology. 2012 ; Vol. 153, No. 8. pp. 3679-3691.
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