Molecular analysis of INK4 genes in breast carcinomas

  • Authors:
    • K Spirin
    • J Simpson
    • C Miller
    • H Koeffler
  • View Affiliations

  • Published online on: October 1, 1997     https://doi.org/10.3892/ijo.11.4.737
  • Pages: 737-744
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Abstract

Cell cycle regulators have recently been implicated in oncogenic transformation of cells, including the cyclins active in the G1 phase of the cell cycle and their respective cyclin-dependent kinases (CDK) whose activities are regulated by a set of inhibitors of CDK (CDKI). Since CDKIs can inhibit cell proliferation, they may have a role as tumor suppressor genes. To determine if alterations of CDKI genes may be involved in tumorigenesis of breast cancer, we examined the mutational status of p16(INK4A), p15(INK4B), p18(INK4C), p19(INK4D) CDKI genes in 36 primary breast carcinomas and 9 breast cancer cell lines using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), direct DNA sequencing, and Southern blot analysis. Furthermore, amplification of cyclin D1, D2, D3 genes were also examined in these samples. One mutation of p15(INK4B) gene occurred, resulting in change of aspartic acid to asparagine at codon 85. Since aspartic acid at this position is conserved between all four human and murine INK4 proteins, this missense mutation may have functional significance. The sample with a p15(INK4B) point mutation was accompanied by amplification of the cyclin D1 gene. A deletion of the p18(INK4C) gene was found in a primary tumor. Three deletions of the p16(INK4A) gene and two deletions of the p15(INK4B) gene were found in the cell lines. Also, we found amplification of the p15(INK4B) and p16(INK4A) loci in a clinical sample as well as amplification of the p19(INK4D) in another sample, and amplification of the myeloperoxidase (MPO) gene in one cell line and two primary tumors. We suspect that a critical gene for breast cancer is amplified near the MPO gene. These data indicate that CDKI mutations are moderately rare in breast cancer and are often associated with the simultaneous alteration of more than one cell-cycle regulatory gene.

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October 1997
Volume 11 Issue 4

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

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Spandidos Publications style
Spirin K, Simpson J, Miller C and Koeffler H: Molecular analysis of INK4 genes in breast carcinomas. Int J Oncol 11: 737-744, 1997
APA
Spirin, K., Simpson, J., Miller, C., & Koeffler, H. (1997). Molecular analysis of INK4 genes in breast carcinomas. International Journal of Oncology, 11, 737-744. https://doi.org/10.3892/ijo.11.4.737
MLA
Spirin, K., Simpson, J., Miller, C., Koeffler, H."Molecular analysis of INK4 genes in breast carcinomas". International Journal of Oncology 11.4 (1997): 737-744.
Chicago
Spirin, K., Simpson, J., Miller, C., Koeffler, H."Molecular analysis of INK4 genes in breast carcinomas". International Journal of Oncology 11, no. 4 (1997): 737-744. https://doi.org/10.3892/ijo.11.4.737