Ept7, a quantitative trait locus that controls estrogen-induced pituitary lactotroph hyperplasia in rat, is orthologous to a locus in humans that has been associated with numerous cancer types and common diseases

Abstract

Pituitary adenoma is a common intracranial neoplasm that is observed in approximately 10% of unselected individuals at autopsy. Prolactin-producing adenomas, i.e., prolactinomas, comprise approximately 50% of all pituitary adenomas and represent the most common class of pituitary tumor. Multiple observations suggest that estrogens may contribute to development of prolactinoma; however, direct evidence for a causal role of estrogens in prolactinoma etiology is lacking. Rat models of estrogen-induced prolactinoma have been utilized extensively to identify the factors, pathways and processes that are involved in pituitary tumor development. The objective of this study was to localize to high resolution Ept7 (Estrogen-induced pituitary tumor), a quantitative trait locus (QTL) that controls lactotroph responsiveness to estrogens and was mapped to rat chromosome 7 (RNO7) in an intercross between BN and ACI rats. Data presented and discussed herein localize the Ept7 causal variant(s) to a 1.91 Mb interval of RNO7 that contains two protein coding genes, A1bg and Myc, and Pvt1, which yields multiple non-protein coding transcripts of unknown function. The Ept7 orthologous region in humans is located at 8q24.21 and has been linked in genome wide association studies to risk of 8 distinct epithelial cancers, including breast, ovarian, and endometrial cancers; 3 distinct types of B cell lymphoma; multiple inflammatory and autoimmune diseases; and orofacial cleft defects. In addition, the Ept7 locus in humans has been associated with variation in normal hematologic and development phenotypes, including height. Functional characterization of Ept7 should ultimately enhance our understanding of the genetic etiology of prolactinoma and these other diseases.

[Retracted] Exploration of the Effects of TGF‐β Pathway‐Based Pituitary Tumor of Rats on GH3 Cell Line after Intervention with Different Concentrations of TGZ

“…An extensive number of studies in concerning fields have confirmed that there are many pathological factors involved in the occurrence and growth of invasive pituitary adenomas. However, the exact mechanism remains to be elucidated by further studies in order to treat invasive pituitary adenomas at the molecular level [ 10 ].…”

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…The interstrain variation in PRL cell responsiveness to estrogens has also been examined in genetic studies. Genetic variants that reside within Ept7 (estrogen-induced pituitary tumor, a quantitative trait locus mapped to rat chromosome 7 that is orthologous to an interval within the 8q24.21 region of the human genome, associated with risk of numerous cancer types and other common diseases) have been implicated in lactotropic cell responsiveness to estrogens [90]. In particular, Ept7 locus carries Myc, a well-known proto-oncogene, and estrogens enhance Myc expression in the rat anterior pituitary gland [46] (Figure 1).…”