EXPRESSION OF RETINOIC ACID RECEPTOR-BETA-2 MESSENGER-RNA IN NORMAL CERVICAL EPITHELIUM AND CERVICAL SQUAMOUS-CELL CARCINOMA

Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several h uman cancers. Retinoid/interferon combinations have demonstrated activ ity in advanced stage cervical cancer. The objective of this study was to quantify and localize the expression of RAR-beta 2, a retinoid ind ucible receptor, in normal cervix and cervical squamous cell carcinoma by quantitative reverse transcriptase-polymerase chain reaction (RT-P CR) and in situ RT-PCR. Specimens where obtained from 11 patients enro lled in a clinical trial to test all-trans retinoic acid (tRA) in comb ination with interferon-alpha 2a (IFN-alpha 2a) in the treatment of me tastatic or recurrent cervical carcinoma. Expression of RAR-beta 2 in cervical carcinoma and normal cervix was measured by quantitative RT-P CR. DNA competitors were used to estimate the relative expression leve l of RAR-beta 2. Expression of RAR-beta 2 was examined in normal cervi x by in situ RT-PCR. Expression of RAR-beta 2 in cervical carcinoma ra nged from 0.33 to 1.40 with a mean of 0.89+/-0.13 vs. 1.0+/-0.13 for n ormal cervix (NS) with RAR-beta 2 reduced to less than or equal to 65% in five cases. Irt situ RT-PCR identified RAR-beta 2 most prominently in basal and para-basal epithelial cell layers of normal exocervix; s tromal expression was markedly decreased. This is the first report to localize expression of RAR-beta 2 mRNA in normal cervical epithelium a nd quantify expression in normal cervix and cervical squamous cell car cinoma. Because retinoid receptors are the proximate mediators of reti noid action on gene expression, alteration of their expression or func tion could result in cancer development.