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Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kim, Youn Hee Han, Guang Zou, Changchan Oridate, Nobuhiko Walsh, Garrett Lyndon Xu, Xìao-Chun Ki, Waun Lotan, Reuben |
| Copyright Year | 1995 |
| Abstract | Retinoids have demonstrated activity in the prevention of second primary tumors in patients with non-small cell lung cancer (NSCLC). They also contribute to the normal growth and differentiation of human bronchial epithelial (HBE) cells. Because retinoids mediate their actions through retinoid nuclear receptors (RARs and RXRs), aberrant signaling through retinoid receptors could contribute to lung carcinogenesis. Using a lung carcinogenesis model consisting of normal, premalignant, and malignant HBE cells, we examined all-trans retinoic acid (t-RA)-induced changes in cellular growth. These studies revealed that t-RA treatment inhibited the growth of normal HBE cells, but premalignant and malignant HBE cells were relatively resistant to t-RA. Coincident with the development of retinoid refractoriness, basal expression of the retinoic acid nuclear receptor beta (RAR-beta) increased. Analysis of receptor function by gel shift and transient transfection assays of normal, premalignant, and malignant HBE cells demonstrated that receptor-DNA binding and transcriptional activation properties were intact in the t-RA-refractory malignant HBE cells. To compare these findings to NSCLCs in patients, we investigated retinoid receptor expression in NSCLC biopsies. A subset of the tumors expressed RAR-beta, reflecting the RAR-beta expression observed in the malignant HBE cells in culture. These findings demonstrate that retinoid receptor function was intact in the t-RA-refractory malignant HBE cell line, suggesting that the defect in retinoid signaling in this lung carcinogenesis model is not intrinsic to the retinoid receptors. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/55/23/5603.full.pdf |
| PubMed reference number | 7585641v1 |
| Volume Number | 55 |
| Issue Number | 23 |
| Journal | Cancer research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adrenergic beta-Agonists Adrenergic beta-Antagonists Biopsy Carcinogenesis HBE1 gene HBE1 wt Allele Neoplasms Non-Small Cell Lung Carcinoma Patients Precancerous Conditions Receptors, Nuclear Refractory anemia with ringed sideroblasts Retinoic Acid Receptor Retinoid X Receptor gamma Retinoid X Receptors Retinoids Small cell carcinoma of lung Structure of parenchyma of lung Subgroup Transcription, Genetic Transcriptional Activation Tretinoin cell growth dna binding primary tumor |
| Content Type | Text |
| Resource Type | Article |
