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Conference Paper: The tumor suppressor Phosphatase and Tensin Homolog (PTEN) suppressed cancer cell invasiveness, possibly via interaction with ROCK, in liver cancer

TitleThe tumor suppressor Phosphatase and Tensin Homolog (PTEN) suppressed cancer cell invasiveness, possibly via interaction with ROCK, in liver cancer
Authors
Issue Date2008
PublisherAmerican Association for Cancer Research
Citation
AACR 99th Annual Meeting, San Diego, CA, 12-16 April 2008. In Cancer Research, 2008, v. 68 n. 9S, Abstract no. 354 How to Cite?
AbstractPhosphatase and tensin homolog (PTEN) is one of the most important tumor suppressors that functions to shut down the cell survival PI3K/AKT signalling pathway, which has been linked to carcinogenesis. To confirm the aberrant deregulation of PTEN/AKT pathway in hepatocellular carcinoma (HCC), the second commonest fatal cancer in Hong Kong, we investigated PTEN expression levels and characterized its functions in HCC. We have examined the protein expression of PTEN in both HCC cells and paired human HCC samples using western blot analysis. Different expression levels of PTEN were observed in a panel of HCC cell lines. Interestingly, a higher PTEN expression was found in H2P HCC cell line, a cell line derived from a human primary HCC, than its metastatic counterpart, H2M, which was derived from the tumor metastasis from the liver of the same patient. In human HCC, we have found frequent (58%) underexpression of PTEN at protein level in HCC, as compared with their corresponding non-tumorous livers. In order to examine the loss of function effects, stable knockdown of PTEN in SMMC 7721 and BEL7402 HCC cell lines with a higher endogenous PTEN was established as an in vitro model. Stable knockdown of PTEN in both SMMC and BEL7402 cells significantly enhanced cell invasiveness, as shown by Matrigel cell invasion assay. This implicates that loss of PTEN may promote tumor metastasis, and this finding has not been reported in HCC. In line with this finding, mouse embryonic fibroblasts (MEF) with wild-type PTEN and its knockout counterpart were used to dissect the PTEN defective downstream pathway. Interestingly, in the PTEN knockout MEFs lacking PTEN expression, the protein levels of phospho-Akt, ROCK 1 and ROCK 2 were significantly upregulated. ROCK is an immediate down-stream effector of Rho and a key regulator of many cytoskeletal events, and is implicated in cancer cell metastasis. The upregulation of ROCK 1 and ROCK 2 in PTEN knockout MEFs suggests a possible regulatory mechanism between PTEN and ROCK. Our data implicate a role of PTEN in hepatocarcinogenesis and potentially in tumor metastasis. (This study was supported by a Hong Kong Research Grants Council Central Allocation Grant HKU 1/06C and a Hong Kong RGC grant HKU 7436/04M)
Persistent Identifierhttp://hdl.handle.net/10722/104677
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorWong, LTen_HK
dc.contributor.authorYau, TOen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-25T22:02:52Z-
dc.date.available2010-09-25T22:02:52Z-
dc.date.issued2008en_HK
dc.identifier.citationAACR 99th Annual Meeting, San Diego, CA, 12-16 April 2008. In Cancer Research, 2008, v. 68 n. 9S, Abstract no. 354-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104677-
dc.description.abstractPhosphatase and tensin homolog (PTEN) is one of the most important tumor suppressors that functions to shut down the cell survival PI3K/AKT signalling pathway, which has been linked to carcinogenesis. To confirm the aberrant deregulation of PTEN/AKT pathway in hepatocellular carcinoma (HCC), the second commonest fatal cancer in Hong Kong, we investigated PTEN expression levels and characterized its functions in HCC. We have examined the protein expression of PTEN in both HCC cells and paired human HCC samples using western blot analysis. Different expression levels of PTEN were observed in a panel of HCC cell lines. Interestingly, a higher PTEN expression was found in H2P HCC cell line, a cell line derived from a human primary HCC, than its metastatic counterpart, H2M, which was derived from the tumor metastasis from the liver of the same patient. In human HCC, we have found frequent (58%) underexpression of PTEN at protein level in HCC, as compared with their corresponding non-tumorous livers. In order to examine the loss of function effects, stable knockdown of PTEN in SMMC 7721 and BEL7402 HCC cell lines with a higher endogenous PTEN was established as an in vitro model. Stable knockdown of PTEN in both SMMC and BEL7402 cells significantly enhanced cell invasiveness, as shown by Matrigel cell invasion assay. This implicates that loss of PTEN may promote tumor metastasis, and this finding has not been reported in HCC. In line with this finding, mouse embryonic fibroblasts (MEF) with wild-type PTEN and its knockout counterpart were used to dissect the PTEN defective downstream pathway. Interestingly, in the PTEN knockout MEFs lacking PTEN expression, the protein levels of phospho-Akt, ROCK 1 and ROCK 2 were significantly upregulated. ROCK is an immediate down-stream effector of Rho and a key regulator of many cytoskeletal events, and is implicated in cancer cell metastasis. The upregulation of ROCK 1 and ROCK 2 in PTEN knockout MEFs suggests a possible regulatory mechanism between PTEN and ROCK. Our data implicate a role of PTEN in hepatocarcinogenesis and potentially in tumor metastasis. (This study was supported by a Hong Kong Research Grants Council Central Allocation Grant HKU 1/06C and a Hong Kong RGC grant HKU 7436/04M)-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleThe tumor suppressor Phosphatase and Tensin Homolog (PTEN) suppressed cancer cell invasiveness, possibly via interaction with ROCK, in liver canceren_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYau, TO: yauto@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.hkuros146626en_HK

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