Differential expression of the cyclin-dependent kinase inhibitors p16 and p21 in the human melanocytic system

Oncogene. 1996 Mar 7;12(5):1069-75.


To determine whether loss or inactivation of the putative tumor-suppressor gene, p16, represents an initiating or a secondary event in the progression of human melanoma, we evaluated the status of this gene in early and advanced-stage melanomas of sporadic origin. The results of this analysis revealed p16 deletions in 4/6 primary and 6/14 metastatic melanoma cell lines but not in 3/3 metastatic melanoma specimens. Surprisingly, p16 deletions were also detected in 8/8 benign compound nevi and in 1/3 normal human melanocyte isolates. To investigate whether these deletions in benign and malignant stages of the human melanocytic system were specific for p16, we analysed the same specimens and cell lines for expression of p21, another cyclin-dependent kinase inhibitor and potential tumor suppressor. In contrast to p16, expression of p21 was detected in 3/3 melanocytes, in 3/3 benign nevi, and in greater than 50% of malignant melanoma cell lines and specimens. Finally, because of the recently documented inverse relationship between expression of p16 and pRb protein in a variety of tumor cell lines, we analysed some of the p16-positive and negative melanoma cell lines for the presence of pRb protein. The results demonstrated pRb protein in each of these cell lines. Taken together, although this study revealed deletions of the p16 gene in a significant number of sporadic primary and metastatic melanoma cell lines, they were also detected in benign nevus specimens and in some normal human melanocyte isolates. Thus, these findings cast some doubt on the role of this gene as being causal to the onset and progression of human melanoma, in particular, sporadic melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Cyclins / metabolism
  • DNA, Neoplasm / analysis
  • Gene Deletion*
  • Genes, Tumor Suppressor / genetics*
  • Humans
  • Melanocytes / metabolism
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Proliferating Cell Nuclear Antigen / analysis*
  • Proliferating Cell Nuclear Antigen / genetics
  • RNA, Messenger / analysis
  • Retinoblastoma Protein / analysis*
  • Tumor Cells, Cultured


  • CDKN1A protein, human
  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Retinoblastoma Protein