IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma
<p>Abstract</p> <p>Background</p> <p>IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carci...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-10-01
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| Series: | BMC Gastroenterology |
| Online Access: | http://www.biomedcentral.com/1471-230X/10/125 |
| _version_ | 1818750416047833088 |
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| author | Odze Robert D Li Zhigang Gnatenko Dmitri V Khurana Hema White Colin D Sacks David B Schmidt Valentina A |
| author_facet | Odze Robert D Li Zhigang Gnatenko Dmitri V Khurana Hema White Colin D Sacks David B Schmidt Valentina A |
| author_sort | Odze Robert D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC.</p> <p>Methods</p> <p>IQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of the <it>Iqgap2 </it>promoter was determined by pyrosequencing of bisulfite-treated genomic DNA.</p> <p>Results</p> <p>IQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although the <it>Iqgap2 </it>promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6).</p> <p>Conclusions</p> <p>We conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of the <it>Iqgap2 </it>promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.</p> |
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| id | doaj.art-579d8c4e2484411795f1f4ba6196d21c |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-18T04:19:19Z |
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| series | BMC Gastroenterology |
| spelling | doaj.art-579d8c4e2484411795f1f4ba6196d21c2022-12-21T21:21:16ZengBMCBMC Gastroenterology1471-230X2010-10-0110112510.1186/1471-230X-10-125IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular CarcinomaOdze Robert DLi ZhigangGnatenko Dmitri VKhurana HemaWhite Colin DSacks David BSchmidt Valentina A<p>Abstract</p> <p>Background</p> <p>IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC.</p> <p>Methods</p> <p>IQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of the <it>Iqgap2 </it>promoter was determined by pyrosequencing of bisulfite-treated genomic DNA.</p> <p>Results</p> <p>IQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although the <it>Iqgap2 </it>promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6).</p> <p>Conclusions</p> <p>We conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of the <it>Iqgap2 </it>promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.</p>http://www.biomedcentral.com/1471-230X/10/125 |
| spellingShingle | Odze Robert D Li Zhigang Gnatenko Dmitri V Khurana Hema White Colin D Sacks David B Schmidt Valentina A IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma BMC Gastroenterology |
| title | IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma |
| title_full | IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma |
| title_fullStr | IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma |
| title_full_unstemmed | IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma |
| title_short | IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma |
| title_sort | iqgap1 and iqgap2 are reciprocally altered in hepatocellular carcinoma |
| url | http://www.biomedcentral.com/1471-230X/10/125 |
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