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Conference Paper: Kinesin family member 7 (KIF7) in endometrial and ovarian cancers

TitleKinesin family member 7 (KIF7) in endometrial and ovarian cancers
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research
Citation
The 100th Annual Meeting of the American Association for Cancer Research, Denver, CO, 18 - 22 April 2009. In Cancer Research, 2009, v. 69, Abstract no. 5326 How to Cite?
AbstractKIF7 is a kinesin superfamily member important in the intracellular transport system and is involved in the Hedgehog signaling pathway. The Hedgehog signaling pathway and some kinesin members have been demonstrated to be associated with human carcinogenesis. In this study, the expression status as well as genetic and epigenetic alterations of KIF7 in endometrial and ovarian cancers was examined. Five endometrial and nine ovarian cancer cell lines as well as 40 endometrial and ovarian cancer cases with available paired tumor and non-tumor tissues were studied. All endometrial and 5 out of 9 ovarian cancer cell lines demonstrated absent to weak KIF7 mRNA expression. KIF7 was also found to be significantly reduced in the endometrial and ovarian cancers comparing to the non-tumors (P<0.02, Wilcoxon test). Ectopic expression of KIF7 in ovarian cancer cell line by transfection resulted in significant (60%) suppression of colony formation. Using bisulfite sequencing and methylation specific PCR (MSP), KIF7 promoter methylation was found in all of the endometrial and ovarian cancer cell lines. Treatment of endometrial (HEC1A) and ovarian (OVCA433) cancer cell lines by 5-aza-2'-deoxycytidine, a DNA methytransferase inhibitor, could significantly restore and elevate the KIF7 expression in both cell lines confirming that promoter methylation plays a role in suppression of KIF7. MSP analysis showed that the methylated allele of KIF7 was present in all endometrial and ovarian cancer and non-tumor samples. The KIF7 promoter methylation was also observed in blood DNA samples from healthy males. In contrast, the unmethylated alleles were found in only 50% of the ovarian cancers while it was present in all non-tumor samples. Almost all the ovarian cancers with only hypermethylated allele of KIF7 demonstrated reduced KIF7 expression. Direct-sequencing KIF7 cDNA from the cancer cell lines discovered one novel spliced variant and one inframe deletion. Whether these spliced and deletion variants function as the wild-type and whether these variants are rare isoforms will be further examined by functional assays and screening in the clinical samples respectively. In contrast, allelic loss of KIF7 was found to be infrequent in ovarian cancers. Our findings suggested that KIF7 may be a tumor suppressor gene and play a role in ovarian and endometrial carcinogenesis. We are the first group to demonstrate the aberrant expression and methylation patterns in these cancers. The current study opens a new avenue for studying the role of KIF7 in human cancers.
Persistent Identifierhttp://hdl.handle.net/10722/63527
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLiao, Xen_HK
dc.contributor.authorChan, YKen_HK
dc.contributor.authorChan, ILSen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorSiu, KYen_HK
dc.contributor.authorKhoo, USen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-07-13T04:25:42Z-
dc.date.available2010-07-13T04:25:42Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 100th Annual Meeting of the American Association for Cancer Research, Denver, CO, 18 - 22 April 2009. In Cancer Research, 2009, v. 69, Abstract no. 5326-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/63527-
dc.description.abstractKIF7 is a kinesin superfamily member important in the intracellular transport system and is involved in the Hedgehog signaling pathway. The Hedgehog signaling pathway and some kinesin members have been demonstrated to be associated with human carcinogenesis. In this study, the expression status as well as genetic and epigenetic alterations of KIF7 in endometrial and ovarian cancers was examined. Five endometrial and nine ovarian cancer cell lines as well as 40 endometrial and ovarian cancer cases with available paired tumor and non-tumor tissues were studied. All endometrial and 5 out of 9 ovarian cancer cell lines demonstrated absent to weak KIF7 mRNA expression. KIF7 was also found to be significantly reduced in the endometrial and ovarian cancers comparing to the non-tumors (P<0.02, Wilcoxon test). Ectopic expression of KIF7 in ovarian cancer cell line by transfection resulted in significant (60%) suppression of colony formation. Using bisulfite sequencing and methylation specific PCR (MSP), KIF7 promoter methylation was found in all of the endometrial and ovarian cancer cell lines. Treatment of endometrial (HEC1A) and ovarian (OVCA433) cancer cell lines by 5-aza-2'-deoxycytidine, a DNA methytransferase inhibitor, could significantly restore and elevate the KIF7 expression in both cell lines confirming that promoter methylation plays a role in suppression of KIF7. MSP analysis showed that the methylated allele of KIF7 was present in all endometrial and ovarian cancer and non-tumor samples. The KIF7 promoter methylation was also observed in blood DNA samples from healthy males. In contrast, the unmethylated alleles were found in only 50% of the ovarian cancers while it was present in all non-tumor samples. Almost all the ovarian cancers with only hypermethylated allele of KIF7 demonstrated reduced KIF7 expression. Direct-sequencing KIF7 cDNA from the cancer cell lines discovered one novel spliced variant and one inframe deletion. Whether these spliced and deletion variants function as the wild-type and whether these variants are rare isoforms will be further examined by functional assays and screening in the clinical samples respectively. In contrast, allelic loss of KIF7 was found to be infrequent in ovarian cancers. Our findings suggested that KIF7 may be a tumor suppressor gene and play a role in ovarian and endometrial carcinogenesis. We are the first group to demonstrate the aberrant expression and methylation patterns in these cancers. The current study opens a new avenue for studying the role of KIF7 in human cancers.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Research-
dc.titleKinesin family member 7 (KIF7) in endometrial and ovarian cancersen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, YK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailChan, ILS: irenejeff@i-cable.comen_HK
dc.identifier.emailWong, KY: kywonga@HKUCC.hku.hken_HK
dc.identifier.emailWong, ESY: esywong@hkucc.hku.hken_HK
dc.identifier.emailChan, HY: hoiyanhk@gmail.comen_HK
dc.identifier.emailSiu, KY: mkysiu@hkusua.hku.hken_HK
dc.identifier.emailKhoo, US: uskhoo@pathology.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authorityChan, YK=rp00453en_HK
dc.identifier.authoritySiu, KY=rp00275en_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.hkuros157427en_HK

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