Wild-type p16INK4a suppresses cell growth, telomerase activity and DNA repair in human breast cancer MCF-7 cells

  • Authors:
    • Jianming Duan
    • Zhong Chen
    • Pinghu Liu
    • Zongyu Zhang
    • Tanjun Tong
  • View Affiliations

  • Published online on: June 1, 2004     https://doi.org/10.3892/ijo.24.6.1597
  • Pages: 1597-1605
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Abstract

p16INK4a, a cell cycle inhibitor that inhibits cyclin-dependent kinase 4 (cdk4) and cdk6, has been found as the tumor suppressor gene and is frequently deleted, methylated or mutated in many malignancies. Since p16INK4a is also a key element controlling cellular senescence and other functions, we hypothesized that p16INK4a induced tumor suppression may not be limited to the inhibition of cdks. To investigate the role of p16INK4a in tumor suppression and the potential interaction between p16INK4a and other cellular controlling elements, such as telomerase activity and DNA repair ability, the full-length of p16INK4a cDNA was cloned into a retroviral vector and introduced into human breast cancer MCF-7 cells that were previously demonstrated to harbor homozygous deletions of the p16INK4a gene. Stable expression of p16INK4a suppressed the malignant phenotype in MCF-7 cells, including cell proliferation, anchorage-independent growth, G1/G0 cell cycle arrest, and the blockage of pRB phosphorylation. In addition, expression of p16INK4a suppressed telomerase activity and restored the telomere shortening process, and decreased cell DNA repair ability and sensitized cells to the DNA damage reagent. Our data suggest that the wild-type p16INK4a plays an important role in suppression of tumor malignancy, not only by inhibiting cell proliferation through cell cycle arrest, but also by inhibiting other cellular controlling mechanisms, such as telomerase activity and DNA repair capacity.

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June 2004
Volume 24 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Duan J, Chen Z, Liu P, Zhang Z and Tong T: Wild-type p16INK4a suppresses cell growth, telomerase activity and DNA repair in human breast cancer MCF-7 cells. Int J Oncol 24: 1597-1605, 2004.
APA
Duan, J., Chen, Z., Liu, P., Zhang, Z., & Tong, T. (2004). Wild-type p16INK4a suppresses cell growth, telomerase activity and DNA repair in human breast cancer MCF-7 cells. International Journal of Oncology, 24, 1597-1605. https://doi.org/10.3892/ijo.24.6.1597
MLA
Duan, J., Chen, Z., Liu, P., Zhang, Z., Tong, T."Wild-type p16INK4a suppresses cell growth, telomerase activity and DNA repair in human breast cancer MCF-7 cells". International Journal of Oncology 24.6 (2004): 1597-1605.
Chicago
Duan, J., Chen, Z., Liu, P., Zhang, Z., Tong, T."Wild-type p16INK4a suppresses cell growth, telomerase activity and DNA repair in human breast cancer MCF-7 cells". International Journal of Oncology 24, no. 6 (2004): 1597-1605. https://doi.org/10.3892/ijo.24.6.1597