Endocrine Abstracts

MicroRNAs are highly conserved non-coding RNAs that regulate diverse cellular processes. Altered microRNA expression is observed in many human cancers and microRNAs may have tumour suppressor or oncogenic properties. One group of putative tumour suppressor microRNAs is the let-7 family whose expression is reduced in several human tumours, and which inhibit the expression of several oncogenes including HMGA2 and K-Ras. Let-7 expression have also been observed to be reduced in human pituitary tumours, including prolactinomas, corticotrophinomas and non-functioning adenomas, although the functional significance of this has not been assessed. We therefore examined the expression of let-7a and its putative targets Hmga2 and K-ras in anterior pituitary tumours that developed in mice deleted for a multiple endocrine neoplasia type 1 (Men1^+/−) allele. The anterior pituitary tumours that develop in Men1^+/− mice include prolactinomas, somatotrophinomas, corticotrophinomas and non-functioning adenomas. Mice were kept in accordance with UK Home Office welfare guidelines and project licence restrictions. Total RNA was extracted from pituitaries of five age-matched wild-type (Men1^+/+) and five Men1^+/− mice and quantitative reverse transcriptase-PCR performed to measure microRNA and target mRNA expression. Compared to Men1^+/+ pituitary tissue, Men1^+/− pituitary tumours showed significant downregulation of let-7a expression (−1.7 fold change, P<0.05). Hmga2 expression was similar in Men1^+/+ pituitaries and Men1^+/− pituitary tumours but a significant increase in K-ras mRNA expression (+1.5 fold change, P<0.05) was observed in Men1^+/− pituitary tumours compared to Men1^+/+ pituitary tissue. Thus, our studies, which demonstrate a reduced let-7a expression in Men1^+/− mouse pituitary tumours, together with an increased expression of the oncogene K-ras provide insights about the role of the microRNA let-7a and its target gene K-ras in pituitary tumourigenesis.