p16 and p16β are potent growth suppressors of head and neck squamous carcinoma cells in vitro

William H. Liggett, Duane A. Sewell, James Rocco, Steven A. Ahrendt, Wayne Koch, David Sidransky

Research output: Contribution to journalArticle

Abstract

p16 (CDKN2/MTS1/p16(INK4a)) is frequently deleted, methylated, or mutated in many malignancies including squamous cell carcinoma of the head and neck (HNSCC). p16β is an alternative transcript derived from a newly described exon (exon 1β) located more than 15 kb 5' to exon 1 of p16. Moreover, the p16β transcript theoretically encodes a protein distinct from p16 derived from a divergent reading frame putatively initiated in exon 1β. To test the contribution of both of these transcripts in carcinogenesis, full-length cDNA of p16 and p16β were cloned in separate vector constructs and then transfected into HNSCC cell lines characterized for p16 status (p16[+/+], p16[mut/-], and p16[methylated]). Transfection of either p16 or p16β resulted in marked growth inhibition in all three HNSCC lines tested, regardless of p16 status. However, p16β but not p16 inhibited the growth of HeLa cells, a cell line with inactive pRB due to expression of E7 papillomavirus protein. Moreover, transfection of all three HNSCC lines with either p16 or p16β resulted in a marked increase in cells in G0-G1 consistent with a cell cycle arrest in G1. These data are consistent with the hypothesis that p16 and p16β are growth-inhibitory genes active in HNSCC and that both act by blocking progression through the G1-S transition of the cell cycle. Furthermore, the suppressive effects of p16β on HeLa growth suggest that p16β mediates its effect independently from pRB.

Original languageEnglish (US)
Pages (from-to)4119-4123
Number of pages5
JournalCancer Research
Volume56
Issue number18
StatePublished - Sep 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'p16 and p16β are potent growth suppressors of head and neck squamous carcinoma cells in vitro'. Together they form a unique fingerprint.

  • Cite this