Loss of Caveolin 2 in endometrial adenocarcinoma

A46

Caveolin disregulation has been noted in several cancer types and has been implicated in suppressing tumorigenesis. Endometrial cancer gene expression microarray data has previously indicated a distinct down-regulation of Caveolins in endometrial cancers consistent with a possible tumor suppressor function. The objective of this study was to validate this observation at the protein level and to perform an initial functional examination of Caveolins and their role in suppressing endometrial cancer growth.
 In order to examine possible mechanisms of Caveolin down-regulation we evaluated CAV1 and CAV2 expression in a panel of endometrial cancer cell lines. CAV1 was expressed in all five cell lines whereas CAV2 message was absent in four of five cell lines. To examine whether epigenetic modifications were involved in suppressing CAV2 message we examined CAV2 levels following 5-aza-2'-deoxycytidine treatment. CAV2 levels dramatically increased following treatment indicating that epigenetic modification of this locus was involved in silencing CAV2. We examined CAV1 and CAV2 levels in paraffin embedded specimens of normal and cancerous endometrium. CAV1 was expressed in normal endometrial stroma and was absent in epithelial cells. CAV2 was expressed in normal epithelial cells and absent in stroma. Endometrial cancers exhibited an almost universal loss of CAV2. Furthermore, we examined the effect of CAV2 expression on colony formation in the CAV2 null HHUA endometrial cancer cellline. CAV2 significantly inhibited colony formation in HHUA cells as compared to empty vector (negative control) and was similar to TP53 (positive control, HHUA cell are TP53 mutant).
 Immunohistochemical analysis of endometrial samples confirmed loss ofCAV2 in endometrial cancer epithelial cells. CAV2 levels were readily restored in endometrial cancer cells following treatment with agents affecting methylation. Furthermore, CAV2 inhibited colony formation when restored to HHUA cells. These data support the contention that CAV2 loss is common in endometrial cancer and that loss of CAV2 is consistent with tumor suppressive ability of the gene.