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 Martin 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

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Exons
Growth
Transfection
Papillomavirus E7 Proteins
G1 Phase Cell Cycle Checkpoints
Cell Line
Reading Frames
HeLa Cells
Cell Cycle
Carcinogenesis
Complementary DNA
In Vitro Techniques
Carcinoma, squamous cell of head and neck
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

p16 and p16β are potent growth suppressors of head and neck squamous carcinoma cells in vitro. / Liggett, William H.; Sewell, Duane A.; Rocco, James; Ahrendt, Steven A.; Koch, Wayne Martin; Sidransky, David.

In: Cancer Research, Vol. 56, No. 18, 15.09.1996, p. 4119-4123.

Research output: Contribution to journalArticle

Liggett, WH, Sewell, DA, Rocco, J, Ahrendt, SA, Koch, WM & Sidransky, D 1996, 'p16 and p16β are potent growth suppressors of head and neck squamous carcinoma cells in vitro', Cancer Research, vol. 56, no. 18, pp. 4119-4123.
Liggett, William H. ; Sewell, Duane A. ; Rocco, James ; Ahrendt, Steven A. ; Koch, Wayne Martin ; Sidransky, David. / p16 and p16β are potent growth suppressors of head and neck squamous carcinoma cells in vitro. In: Cancer Research. 1996 ; Vol. 56, No. 18. pp. 4119-4123.
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