High Expression of Cyclin E and G1 CDK and Loss of Function of p57KIP2 Are Involved in Proliferation of Malignant Sporadic Adrenocortical Tumors Export

@article{citeulike:5879474, abstract = {Maternal loss of heterozygosity (LOH) of the 11p15 region and overexpression of the insulin-like growth factor (IGF)-II gene are associated with the malignant phenotype in sporadic adrenocortical tumors. In the imprinted 11p15 region, the p57KIP2 gene is maternally expressed and encodes a cyclin-dependent kinase (CDK) inhibitor involved in G1/S phase of the cell cycle. We hypothesized that maternal LOH in malignant adrenocortical tumors could be responsible for loss of p57KIP2 gene expression and, thus, could favor progression through the cell cycle. We investigated 3 normal adrenals, 31 adrenocortical tumors [11 tumors with normal expression of the IGF-II gene (mainly benign) and 20 with IGF-II gene overexpression (mainly malignant)], and the human adrenocortical tumor cell line NCI H295R for expression of the p57KIP2 gene, G1 cyclins (cyclin D2 and E) and G1 CDK (CDK2, CDK3 and CDK4) protein contents and for kinase activity of G1 cyclin-CDK complexes. The expression of p57KIP2, G1 cyclins, and G1 CDKs in benign tumors was similar to that in normal adrenal tissues, as were kinase activities of G1 cyclin-CDK complexes. By contrast, abrogation of the p57KIP2 gene expression and increased expression of G1 cyclins (cyclin E) and G1 CDKs (CDK2 and CDK4) were associated with high activity of G1 cyclin-CDK complexes in malignant tumors and in the H295R cell line. These data suggest that the p57KIP2 gene might act as a tumor suppressor gene in adrenocortical tumors. Maternal LOH with duplication of the paternal allele or pathological functional imprinting of the 11p15 region are responsible for loss of expression of the p57KIP2 gene and increased expression of the IGF-II gene. Consequently, both events favor cell proliferation in malignant adrenocortical tumors. 10.1210/jc.85.1.322}, author = {Bourcigaux, Nathalie and Gaston, Veronique and Logie, Armelle and Bertagna, Xavier and Le Bouc, Yves and Gicquel, Christine}, citeulike-article-id = {5879474}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/jc.85.1.322}, citeulike-linkout-1 = {http://jcem.endojournals.org/content/85/1/322.abstract}, citeulike-linkout-2 = {http://jcem.endojournals.org/content/85/1/322.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/10634406}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=10634406}, day = {1}, doi = {10.1210/jc.85.1.322}, journal = {J Clin Endocrinol Metab}, keywords = {acc, cell\_cycle, igf2}, month = {January}, number = {1}, pages = {322--330}, posted-at = {2009-10-02 20:05:04}, priority = {2}, title = {High Expression of Cyclin E and G1 CDK and Loss of Function of p57KIP2 Are Involved in Proliferation of Malignant Sporadic Adrenocortical Tumors}, url = {http://dx.doi.org/10.1210/jc.85.1.322}, volume = {85}, year = {2000} }

TY - JOUR ID - citeulike:5879474 L3 - citeulike-article-id:5879474 N2 - Maternal loss of heterozygosity (LOH) of the 11p15 region and overexpression of the insulin-like growth factor (IGF)-II gene are associated with the malignant phenotype in sporadic adrenocortical tumors. In the imprinted 11p15 region, the p57KIP2 gene is maternally expressed and encodes a cyclin-dependent kinase (CDK) inhibitor involved in G1/S phase of the cell cycle. We hypothesized that maternal LOH in malignant adrenocortical tumors could be responsible for loss of p57KIP2 gene expression and, thus, could favor progression through the cell cycle. We investigated 3 normal adrenals, 31 adrenocortical tumors [11 tumors with normal expression of the IGF-II gene (mainly benign) and 20 with IGF-II gene overexpression (mainly malignant)], and the human adrenocortical tumor cell line NCI H295R for expression of the p57KIP2 gene, G1 cyclins (cyclin D2 and E) and G1 CDK (CDK2, CDK3 and CDK4) protein contents and for kinase activity of G1 cyclin-CDK complexes. The expression of p57KIP2, G1 cyclins, and G1 CDKs in benign tumors was similar to that in normal adrenal tissues, as were kinase activities of G1 cyclin-CDK complexes. By contrast, abrogation of the p57KIP2 gene expression and increased expression of G1 cyclins (cyclin E) and G1 CDKs (CDK2 and CDK4) were associated with high activity of G1 cyclin-CDK complexes in malignant tumors and in the H295R cell line. These data suggest that the p57KIP2 gene might act as a tumor suppressor gene in adrenocortical tumors. Maternal LOH with duplication of the paternal allele or pathological functional imprinting of the 11p15 region are responsible for loss of expression of the p57KIP2 gene and increased expression of the IGF-II gene. Consequently, both events favor cell proliferation in malignant adrenocortical tumors. 10.1210/jc.85.1.322 IS - 1 JF - J Clin Endocrinol Metab EP - 330 TI - High Expression of Cyclin E and G1 CDK and Loss of Function of p57KIP2 Are Involved in Proliferation of Malignant Sporadic Adrenocortical Tumors VL - 85 SP - 322 KW - acc KW - cell_cycle KW - igf2 AU - Bourcigaux, Nathalie AU - Gaston, Veronique AU - Logie, Armelle AU - Bertagna, Xavier AU - Le Bouc, Yves AU - Gicquel, Christine PY - 2000/01/01/ UR - http://dx.doi.org/10.1210/jc.85.1.322 ER -