5’-CpG Island Promoter Hypermethylation of the CAV-1 Gene in Breast Cancer Patients of Kashmir

Abstract

Background: Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggestedtumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated withinactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devisedthis study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breastcancer progression and development.
Methods: Hypermethylation status of CAV-1 was analyzed by methylationspecific PCR. Loss of expression of the CAV-1 gene was further evaluated by semi-quantitative rt-PCR.
Results:28/130 (21.5%) breast cancer cases showed promoter hypermethylation with reduced CAV-1 expression levelswhen compared with adjacent normal breast tissue. CAV-1 gene hypermethylation was significantly related tomenopausal status, histopathological grade and age.
Conclusion: The rationale of our study is that CAV-1 geneis transcriptionally repressed in breast cancer cells due to hypermethylation. Our results reveal that promoterhypermethylation and loss of expression of the CAV-1 gene is an important alternative mechanism for inactivationof CAV-1 leading to complete gene silencing.

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