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Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RARβ and on retinoid resistance in human squamous carcinoma cells

Oncogene volume 20, pages 6820–6827 (2001)Cite this article

Abstract

Retinoids' effects on cell growth and differentiation are mediated by nuclear retinoid receptors, which are ligand-activated transcription enhancing factors. Because the expression of the retinoic acid receptor β (RARβ) gene, which is located on chromosome 3p24, is diminished in premalignant and malignant tissues it has been proposed that it acts as a tumor suppressor. To test the hypothesis that RARβ loss leads to retinoid resistance, we studied several karyotyped head and neck squamous carcinoma (HNSCC) cell lines (UMSCC-17A, -17B, -22A, -22B, and -38) with deletion of one chromosome 3p arm. RARβ mRNA was neither detected nor induced by retinoic acid in these cells, whereas it was expressed and induced by retinoic acid in two other HNSCC cell lines (1483 and 183) without 3p deletion. Methylation of the RARβ gene promoter was detected in the 17B and 22B cells that failed to express RARβ but no methylation was found in 183A cells that did express RARβ mRNA. Responsiveness of HNSCC cells to several retinoids in assays of growth inhibition and colony formation, was rank ordered as: 22B>1483>38>183>17B. Additionally, retinoid response elements were transactivated in 22B more efficiently than in 17B cells. These results indicate that loss of RARβ expression does not necessarily lead to loss of growth inhibition by retinoids or to a block of retinoid signaling.

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Abbreviations

ATRA:

All-trans-retinoic acid

9-cisRA:

9-cis retinoic acid

RAR:

retinoic acid receptor

RXR:

retinoid X receptor

RARE:

retinoic acid response element

RXRE:

retinoid X response element

CVC:

crystal violet

RT-PCR:

reverse transcription polymerase chain reaction

CAT:

chloramphenicol acetyl transferase

LOH:

loss of heterozygosity.

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Acknowledgements

This study was supported by United States Public Health Service Grant PO1 CA52051 from the National Cancer Institute and P50 DE11906 from the National Institute of Dental and Craniofacial Research. CP Zou was supported by Training Grant R25 CA57730 from the National Cancer Institute (Robert Chamberlain, P.I.). R. Lotan is the incumbent of the Irving and Nadine Mansfield and Robert David Levitt Cancer Research Chair. We thank Dr P Sacks (Memorial Sloan-Kettering Cancer Center, New York, NY, USA) for two HNSCC cell lines and Drs Bollag and Shroot for retinoids.

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Authors and Affiliations

  1. Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Science, The University of Texas, Medical School, Houston, Texas, TX, 77030, USA

    Chang-Ping Zou

  2. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, USA

    Emile M Youssef & Reuben Lotan

  3. Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, USA

    Chang-Chun Zou

  4. Department of Otolaryngology/Head and Neck Surgery, The University of Michigan Cancer Center, Ann Arbor, MI 48109, Michigan, USA

    Thomas E Carey

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  1. Chang-Ping Zou
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Correspondence to Reuben Lotan.

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Zou, CP., Youssef, E., Zou, CC. et al. Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RARβ and on retinoid resistance in human squamous carcinoma cells. Oncogene 20, 6820–6827 (2001). https://doi.org/10.1038/sj.onc.1204846

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