Skp2 overexpression is associated with loss of BRCA2 protein in human prostate cancer.

BRCA2 (breast cancer 2, early onset) is a tumor suppressor gene that confers increased susceptibility for prostate cancer (PCa). Previous in vitro experiments demonstrated that Skp2, an E3 ubiquitin ligase aberrantly overexpressed in PCa, is involved in the proteolytic degradation of BRCA2 in PCa cells, suggesting that the BRCA2-Skp2 interaction may play a role in prostate tumorigenesis. Herein, we investigated BRCA2 and Skp2 expression during PCa development using a prostate TMA.

Loss of BRCA2 promotes prostate cancer cell invasion through up-regulation of matrix metalloproteinase-9.

BRCA2 is a multifunctional tumor suppressor protein which plays critical roles in DNA repair, transcription, and cell proliferation, and the loss of which has been linked to the biology of several types of cancers. Here, on prostate adenocarcinoma specimens from 80 patients, we demonstrate that BRCA2 protein is lost in carcinoma cells compared to normal and hyperplastic prostate epithelium. Using highly metastatic prostate cancer PC-3 cells, we show that while BRCA2 depletion by small-interfering RNA promoted migration onto the extracellular matrix proteins fibronectin, laminin, and collagens, as well as invasion through the reconstituted basement membrane matrix Matrigel by more than 140%, recombinant BRCA2 overexpression decreased both phenomena by 57-80% and changed cell morphology from angular and spindle to round and compact.

Extrapulmonary small cell carcinomas express K homology domain containing protein overexpressed in cancer, but carcinoid tumors do not.

A number of malignancies, including high-grade neuroendocrine carcinomas of the lung, have been reported to express K homology domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor messenger RNA-binding protein (IMP) family also known as L523S and IMP3. KOC acts to promote tumor cell proliferation by enhancing insulin-like growth factor-II protein expression. This study aimed to examine KOC expression pattern in extrapulmonary neuroendocrine tumors.