The role of cell cycle regulatory proteins in the pathogenesis of melanoma

Wei Li; Amira Sanki; Rooshdiya Z Karim; John F Thompson; C Soon Lee; Liqing Zhuang; Stanley W McCarthy; Richard A Scolyer

doi:10.1080/00313020600817951

The role of cell cycle regulatory proteins in the pathogenesis of melanoma

Pathology. 2006 Aug;38(4):287-301. doi: 10.1080/00313020600817951.

Authors

Wei Li¹, Amira Sanki, Rooshdiya Z Karim, John F Thompson, C Soon Lee, Liqing Zhuang, Stanley W McCarthy, Richard A Scolyer

Affiliation

¹ The Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown, Australia.

PMID: 16916716
DOI: 10.1080/00313020600817951

Abstract

The transformation of melanocytes to melanoma cells is characterised by abnormal proliferation resulting from alterations in cell cycle regulatory mechanisms. This occurs through alterations in the two major cell cycle regulatory pathways, the retinoblastoma (Rb) and p53 tumour suppressor pathways. This review summarises the current knowledge of alterations in these two pathways at G1/S transition and specifically the role of the key cell cycle regulatory proteins pRb, p16INK4a (p16), cyclin D1, p27Kip1 (p27), p53 and p21Waf1/Cip1 (p21) in the pathogenesis of melanoma. It also considers their prognostic significance. Current data indicate that alterations of cyclin kinase inhibitor (cdki) levels are implicated in the pathogenesis of melanoma and may be useful prognostic markers. However, large validation studies linked to comprehensive clinical follow up data are necessary to clarify the prognostic significance of cell cycle regulatory proteins in individual patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle / genetics
Cell Cycle / physiology*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / physiology*
Cell Proliferation
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / pathology
Cyclin D1 / genetics
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Disease Progression
Gene Expression Regulation, Neoplastic / genetics
Gene Expression Regulation, Neoplastic / physiology
Humans
Melanoma / genetics
Melanoma / physiopathology*
Prognosis
Retinoblastoma Protein / genetics
Retinoblastoma Protein / metabolism
Skin Neoplasms / genetics
Skin Neoplasms / physiopathology*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p21
Retinoblastoma Protein
Tumor Suppressor Protein p53
Cyclin D1
Cyclin-Dependent Kinase Inhibitor p27