[The expression of Rb, p16 and cyclin D1 in 41 esophageal cancers].
D-type cyclins being considered as oncogenes promote progression of the cell through the G1 phase of the cell cycle by CDK4 mediated phosphorylation of the retinoblastoma protein. The activities of CDK4 is constrained by inhibitors such as p16, the product of the CDKN2 in tumor cells and primary tumors suggests that p16 acts as a tumor suppressor. We examined these proteins and genes by immunohistochemistry and in situ hybridization techniques in 41 primary esophageal cancers. Overexpression of cyclin D1 was revealed in 26/41 samples (63.4%) and also in the mucosa adjacent to the cancers in 10 of 26 cyclin D1 overexpression samples, which also have high levels of cyclin D1. P16 was undetectable in 13 of 41 samples. Interestingly, 17 of 24 Rb positive cancers had no or low p16, while 9 Rb-negative cancers showed high levels of p16. These results suggest that the overexpression of cyclin D1 may be a common molecular abnormality and an early molecular event in esophageal cancer, followed either by Rb loss, as occurred in Rb negative samples, or by loss of p16, as occurred in p16 negative samples. Cyclin D1 overexpression and Rb inactivation can coexist in esophageal cancer. However, there is a reciprocity between Rb inactivation and p16 expression in esophageal cancer. Thus, abnormality in the negative feedback regulatory pathway of cyclin D1/CDK4, Rb and p16 may be involved in the molecular mechanism of esophageal cancer.
Zheng
J
J
Department of Cell Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
Zhou
C
C
Xiao
F
F
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016160:Retinoblastoma Protein / Q000096:biosynthesis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1