Osteocyte density changes in aging and osteoporosis

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Exclusion of the phosphatidylinositol-specific phospholipase C beta3 (PLC beta3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN1) gene

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Exclusion of the phosphatidylinositol-specific phospholipase C ß3 (PLCB3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN1) gene

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Exclusion of the nuclear factor-kappa B3 (RELA) gene as candidate for the multiple endocrine neolasia type 1 (MEN1) gene

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Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development

Activating mutations in the RET proto-oncogene are associated with both familial and sporadic medullary thyroid carcinoma (MTC) development; however, the genetic mechanisms underlying MTC tumorigenesis remain largely unknown. Recen tly, we have identified somatic inactivating mutations in the cell cycle inhibitor gene P18 in human MTC, which coincided with activating RET mutations, suggesting a role for loss of P18 in combination with oncogenic RET in the multistep process of MTC development. Therefore, we crossed transgenic mice expressing oncogenic RET (RET2B) with mice lacking p18 (and p27, another cell cycle inhibitor) and monitored MTC development. RET2B;p18+/-mice and RET2B;p18-/-mice developed MTC with a highly increased incidence compared with their corresponding single mutant littermates. In addition, expression of oncogenic RET causes an earlier age of onset and larger MTCs in p18-/-;p27+/-mice. In a subset of MTCs of RET2B;p18+/-(;p27+/-) mice, p18Ink4cexpression was completely lost. This loss of p18Ink4cexpression correlated with higher proliferation rates as well as with larger MTCs, indicating that loss of p18 in combination with oncogenic RET not only increases the risk for MTC development but also enhances MTC progression. Our data strongly indicate that oncogenic RET and loss of p18 cooperate in the multistep tumorigenesis of MTC

Structure and expression of the human calcitonin/CGRP genes

Recently, we have reported the isolation of cDNA encoding a second human calcitonin gene-related peptide (hCGRP-II) [(1985) FEBS Lett. 183, 403-407]. In this report we describe the isolation and characterization of the gene encoding hCGRP-II. This gene, designated CALC-II, is structurally closely related to the known CALC-I gene encoding human calcitonin (hCT) and hCGRP-I. In constrast to CALC-I, CALC-II does not seem to be alternatively expressed. The formation of a second, hCT-like mRNA by differential splicing of CALC-II transcripts is unlikely in view of the structure of CALC-II, and could not be demonstrated in tissues known to express CALC-I and CALC-II