Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors

Yeul Hong Kim, D. F. Dohi, Ro Han Gil Ro Han, C. P. Zou, N. Oridate, G. L. Walsh, J. C. Nesbitt, X. C. Xu, Ki Hong Waun Ki Hong, R. Lotan, J. M. Kurie

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 β (RAR-β) 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 NSULC biopsies. A subset of the tumors expressed RAR-β, reflecting the RAR-β 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.

Original languageEnglish
Pages (from-to)5603-5610
Number of pages8
JournalCancer Research
Volume55
Issue number23
Publication statusPublished - 1995 Jan 1
Externally publishedYes

Fingerprint

Retinoids
Carcinogenesis
Epithelial Cells
Lung
Tretinoin
Cytoplasmic and Nuclear Receptors
Retinoic Acid Receptors
Growth
Primary Prevention
Non-Small Cell Lung Carcinoma
Transcriptional Activation
Transfection
Neoplasms
Cell Culture Techniques
Gels
Biopsy
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kim, Y. H., Dohi, D. F., Gil Ro Han, R. H., Zou, C. P., Oridate, N., Walsh, G. L., ... Kurie, J. M. (1995). Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors. Cancer Research, 55(23), 5603-5610.

Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors. / Kim, Yeul Hong; Dohi, D. F.; Gil Ro Han, Ro Han; Zou, C. P.; Oridate, N.; Walsh, G. L.; Nesbitt, J. C.; Xu, X. C.; Waun Ki Hong, Ki Hong; Lotan, R.; Kurie, J. M.

In: Cancer Research, Vol. 55, No. 23, 01.01.1995, p. 5603-5610.

Research output: Contribution to journalArticle

Kim, YH, Dohi, DF, Gil Ro Han, RH, Zou, CP, Oridate, N, Walsh, GL, Nesbitt, JC, Xu, XC, Waun Ki Hong, KH, Lotan, R & Kurie, JM 1995, 'Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors', Cancer Research, vol. 55, no. 23, pp. 5603-5610.
Kim YH, Dohi DF, Gil Ro Han RH, Zou CP, Oridate N, Walsh GL et al. Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors. Cancer Research. 1995 Jan 1;55(23):5603-5610.
Kim, Yeul Hong ; Dohi, D. F. ; Gil Ro Han, Ro Han ; Zou, C. P. ; Oridate, N. ; Walsh, G. L. ; Nesbitt, J. C. ; Xu, X. C. ; Waun Ki Hong, Ki Hong ; Lotan, R. ; Kurie, J. M. / Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors. In: Cancer Research. 1995 ; Vol. 55, No. 23. pp. 5603-5610.
@article{802b318f2d5f4e0a83453882f3eca289,
title = "Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors",
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 β (RAR-β) 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 NSULC biopsies. A subset of the tumors expressed RAR-β, reflecting the RAR-β 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.",
author = "Kim, {Yeul Hong} and Dohi, {D. F.} and {Gil Ro Han}, {Ro Han} and Zou, {C. P.} and N. Oridate and Walsh, {G. L.} and Nesbitt, {J. C.} and Xu, {X. C.} and {Waun Ki Hong}, {Ki Hong} and R. Lotan and Kurie, {J. M.}",
year = "1995",
month = "1",
day = "1",
language = "English",
volume = "55",
pages = "5603--5610",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

TY - JOUR

T1 - Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors

AU - Kim, Yeul Hong

AU - Dohi, D. F.

AU - Gil Ro Han, Ro Han

AU - Zou, C. P.

AU - Oridate, N.

AU - Walsh, G. L.

AU - Nesbitt, J. C.

AU - Xu, X. C.

AU - Waun Ki Hong, Ki Hong

AU - Lotan, R.

AU - Kurie, J. M.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - 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 β (RAR-β) 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 NSULC biopsies. A subset of the tumors expressed RAR-β, reflecting the RAR-β 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.

AB - 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 β (RAR-β) 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 NSULC biopsies. A subset of the tumors expressed RAR-β, reflecting the RAR-β 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.

UR - http://www.scopus.com/inward/record.url?scp=0028883558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028883558&partnerID=8YFLogxK

M3 - Article

C2 - 7585641

AN - SCOPUS:0028883558

VL - 55

SP - 5603

EP - 5610

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 23

ER -