RT-PCR and Immunohistochemical Studies of Aromatase Expression in Normal Oral Keratinocytes and Squamous Cell Carcinoma

Abstract

Aromatase is a cytochrome P-450 enzyme responsible for estrogen synthesis. Its expression has been found to be dramatically increased in breast carcinoma tissues, leading to the use of aromatase inhibitors as a major treatment for hormone-dependent breast carcinomas in postmenopausal women in recent years. Aromatase expression has never been investigated in oral mucosal tissues or oral cancers. We previously reported evidence from immunocytochemistry and Western blot analysis suggesting aromatase protein expression in normal oral keratinocytes and oral squamous cell carcinoma (SCC) in cell culture. In our current study, we investigated aromatase mRNA expression of the common coding region (exon 2-3) and the various first exons (I.1, I.4, I.7, I.3, and PII) in oral keratinocytes from 3 normal donors and oral SCC cells in culture by RT-PCR. We found that both normal oral keratinocytes and carcinoma cells expressed the common coding region of aromatase. Carcinoma cells expressed exon I variants I.7, I.3, and PII, whereas none of the 3 normal samples expressed I.3 or PII variants and only 1 expressed variant I.7. We also investigated aromatase expression in archival human normal and neoplastic oral tissues by immunohistochemistry. Aromatase expression was detected in oral epithelium in fibromas and in tumor islands of well differentiated SCC but not in tumor islands of poorly differentiated SCC cells. Our current results indicate that, compared to normal oral keratinocytes, oral SCC cells utilize more promoters for aromatase expression. This may lead to an increased amount of aromatase expression in oral SCC, similar to the situation in breast carcinoma cells.