Loss of cellular retinol-binding protein 1 gene expression in microdissected human ovarian cancer.
OBJECTIVE
We have previously found that cellular retinol-binding protein 1 (CRBP1),involved in retinol transport and metabolism, is down-regulated in an in vitro rat model of ovarian cancer and in several human ovarian cancer cell lines. The aim of this study was to determine the clinical relevance of this change to human ovarian cancer.


METHODS
A cohort of 48 frozen human serous ovarian carcinomas was evaluated for CRBP1 gene expression. Malignant ovarian epithelial cells were selectively procured by laser capture microdissection, and their CRBP1 expression was determined by real-time PCR. Immunohistochemistry for CRBP1 was performed on paraffin sections of ovarian tumors using polyclonal affinity-purified rabbit anti-CRBP1 antibody.


RESULTS
In 35% of ovarian cancer patient samples, there was no detectable CRBP1 expression by real-time PCR. The expression of CRBP1 in microdissected serous ovarian carcinomas was not related to either tumor stage (P = 0.6839) or grade (P = 0.9599). Quantitative PCR results were confirmed by immunohistochemistry using an antibody against CRBP1.


CONCLUSIONS
The loss of CRBP1 expression in clinical ovarian tumor specimens is consistent with our previous findings in the rat model and human ovarian cancer cell lines. It appears to be an early event in ovarian carcinogenesis because there was no statistically significant difference in its frequency between tumor stages and grades. Our findings suggest that the loss of CRBP1 expression contributes to the ovarian cancer oncogenesis via altered vitamin A metabolism.
Cvetković
Dusica
D
Department of Medical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Williams
Stephen J
SJ
Hamilton
Thomas C
TC
D051698:Activating Transcription Factor 2; D000328:Adult; D000368:Aged; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors