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Expression of retinoic acid receptors in squamous cell carcinomas and their possible implication for chemoprevention
1Klinik für Hals-Nasen-Ohrenkranke der Ludwig-Maximilians-Universität, Klinikum Grosshadern, München, Germany.
Abstract:
Retinoic acid and its natural and synthetic analogs (retinoids) affect a wide array of biological processes. Retinoids are used in the treatment of many skin diseases and are promising drugs for several cancers. Most of their actions are thought to result from changes in gene expression which is caused via nuclear retinoic acid receptors and retinoid X receptors. We conducted a study to determine whether the expression of these receptors is different in malignant tumors and tumor cell lines versus normal tissue. We performed reverse transcription PCR from 29 tissue specimens of squamous cell carcinomas and one melanoma of the head and neck, as well as from 13 cell lines established from head and neck cancer. We were looking for the expression pattern of RAR alpha, beta, gamma and RXR alpha. Only RAR gamma was expressed 100% in cell lines and tissue specimens. RAR beta showed 100% expression in tissue specimens whereas 54% expression in cell lines was seen. All other receptors were diminished in their expression. In the positive controls all receptors were expressed at 100%. The expression of RAR alpha and RAR beta was partially lost in cell lines established from squamous cell carcinoma of the head and neck. The 100% expression of RAR beta in tissue samples versus 54% in cell lines can be explained by the clonal growth of malignant cells in cell lines and also possible "contamination" by normal cells in the tissue specimen. In concordance with the literature it seems that RARa and beta play a pivotal role in mediating the response to retinoids.
Insights
Retinoic acid receptors (RARs) are crucial for retinoid drug action. RAR gamma is consistently expressed in head and neck cancers, while RAR alpha and beta expression is often lost in cell lines.
Area of Science:
- Molecular Biology
- Oncology
- Dermatology
Background:
- Retinoids, including retinoic acid, regulate gene expression via nuclear receptors.
- These receptors are crucial for retinoid efficacy in treating skin diseases and cancers.
- Understanding receptor expression in tumors is key to optimizing retinoid-based therapies.
Purpose of the Study:
- To investigate the expression patterns of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in head and neck squamous cell carcinomas and melanoma.
- To compare receptor expression in tumor tissues with established cancer cell lines.
- To identify potential differences in receptor expression that could impact retinoid therapy.
Main Methods:
- Reverse transcription PCR (RT-PCR) was used to analyze gene expression.
- 29 head and neck squamous cell carcinoma tissue specimens and 1 melanoma specimen were analyzed.
- 13 head and neck cancer cell lines were examined for RAR alpha, beta, gamma, and RXR alpha expression.
Main Results:
- RAR gamma demonstrated 100% expression in both tissue specimens and cell lines.
- RAR beta was expressed in 100% of tissue specimens but only 54% of cell lines.
- RAR alpha and RAR beta expression was frequently lost in squamous cell carcinoma cell lines compared to normal tissues.
Conclusions:
- RAR gamma is ubiquitously expressed in head and neck tumors and cell lines.
- Loss of RAR alpha and RAR beta expression in cell lines may be due to clonal selection or normal cell contamination in tissues.
- RAR alpha and RAR beta appear critical for mediating retinoid responses, highlighting their importance in cancer therapy.