Induction of gastrin releasing peptide by all-trans retinoic acid in small cell lung cancer cells

Rajani K. Ravi, Frank M. Scott, Frank Cuttitta, Erich Weber, Gregory P. Kalemkerian, Barry D. Nelkin, Mack Mabry

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


All-trans retinoic acid (RA) has been shown to inhibit cell proliferation while increasing neuroendocrine differentiation in small cell lung cancer (SCLC) cells. RA and related compounds are rapidly becoming integrated into clinical trials to prevent lung cancers and other aerodigestive neoplasms. We found that expression of gastrin releasing peptide (GRP), which can promote lung tumorigenesis in model systems, was increased by RA in SCLC cells which have functional retinoid signaling. In SCLC cells that possess functional GRP receptors, ectopic expression of RARγ increased GRP expression and augmented cloning efficiency, demonstrating that these maneuvers result in biologically active GRP. SCLC cells with defects in RA pathway signaling did not efficiently induce GRP upon RA exposure. In these cells, transfection of RARs rendered the cells competent to induce GRP upon RA exposure. These data show that activation of intact retinoid signaling by RA can induce GRP, a growth factor that can act as a tumor promoter. Our findings suggest the possibility that retinoids may increase, rather than decrease, lung cancer risks in some individuals.

Original languageEnglish (US)
Pages (from-to)497-501
Number of pages5
JournalOncology reports
Issue number2
StatePublished - 1998


  • Lung cancer
  • Retinoic acid receptors
  • Retinoids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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