RGD Reference Report - AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis. - Rat Genome Database

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AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis.

Authors: Kim, JW  Cho, HS  Kim, JH  Hur, SY  Kim, TE  Lee, JM  Kim, IK  Namkoong, SE 
Citation: Kim JW, etal., Lab Invest. 2000 Apr;80(4):587-94.
RGD ID: 1643340
Pubmed: PMID:10780674   (View Abstract at PubMed)

To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display (DD) method to analyze normal cervical tissue, cervical cancer, metastatic lymph node, and cervical cancer cell line. We cloned a 491-bp cDNA fragment, CC231, which was present in metastatic tissue and cervical cancer cell line, but absent in normal cervical and cervical cancer tissues. The 491 bp cDNA fragment has 98% homology to the previously published sequence, AAC-11 (antiapoptosis clone 11). The levels of AAC-11 mRNA expressions in nine normal cervical and nine primary cervical cancer tissues were low. Its expression was higher in three metastatic tissues and five cervical cancer cell lines (HeLa, CaSki, SiHa, CUMC-3, and CUMC-6). Invasion of matrigel and adhesion to laminin by AAC-11 transfected CUMC-6 cells were increased by approximately 2-fold and 4-fold, respectively. Northern blot analysis showed that matrix metalloproteinase (MMP)-2 and membrane type 1 MMP (MT1-MMP) genes were found to be expressed in high levels in AAC-11-transfected cancer cells. But MMP-2 and MT1-MMP were not expressed in cells transfected with vector alone or wild-type cells. AAC-11-transfected cells expressed an elevated level of MMP-2 protein as assessed by immunoblotting. On the contrary, tissue inhibitor of MMP (TIMP-2) expression was detectable in cells transfected with vector alone or wild-type cells, respectively. Its expression was undetectable in AAC-11 transfected cells. In cervical cancer cells transfected with AAC-11, the expression of beta-catenin was up-regulated. These suggest that overexpressions of MMP-2 and MT1-MMP, loss of TIMP-2 expression, and up-regulation of beta-catenin by AAC-11 transfection may contribute to the development of cervical cancer invasion. AAC-11 gene transfection increased cervical cancer cell colonization. The effect of AAC-11 on cultured cervical cancer cells was associated with antiapoptotic process. Approximately 50% of the AAC-11 transfected cells in serum-free medium died after 2 weeks, compared to 1 week for vector alone or wild-type cells. These results suggest that AAC-11 may serve as a candidate metastasis-related and apoptosis-inhibiting gene in human cervical cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervical cancer disease_progressionIEP 1643340mRNA:increased expressionRGD 
cervical cancer disease_progressionISOAPI5 (Homo sapiens)1643340; 1643340mRNA:increased expressionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Api5  (apoptosis inhibitor 5)

Genes (Mus musculus)
Api5  (apoptosis inhibitor 5)

Genes (Homo sapiens)
API5  (apoptosis inhibitor 5)

Objects referenced in this article
Gene ANGPT1 angiopoietin 1 Homo sapiens
Gene Angpt1 angiopoietin 1 Mus musculus
Gene Angpt1 angiopoietin 1 Rattus norvegicus

Additional Information