Human cyclin D1 oncogene and esophageal squamous cell carcinoma.
BACKGROUND
Oncogene activation and tumor suppressor gene inactivation have been implicated in the genetic basis of esophageal squamous cell carcinoma (ESCC). Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parathyroid adenomas and centrocytic lymphomas.


METHODS
Established ESCC cell lines were assayed for cyclin D1 amplification and overexpression by Southern, Northern, and Western blot analyses. In addition, cyclin D1 overexpression was determined in primary tumors and adjacent normal mucosa by differential polymerase chain reaction (PCR) and immunohistochemical staining.


RESULTS
The authors observed that approximately 50% of ESCC cell lines with cyclin D1 DNA amplification also had RNA and protein overexpression. Related genes, cyclin D2 and D3, were not amplified or overexpressed in these cell lines with rare exception. The cyclin D1 protein was able to associate with the cell-cycle-dependent kinases, cdk4 and cdk6, but not always with proliferating cell nuclear antigen in selected cell lines tested, representing a novel finding. In addition, approximately 50% of primary tumors had cyclin D1 overexpression that was not present in adjacent normal mucosa. Cyclin D1 overexpression based on PCR correlated with enhanced cyclin D1 protein nuclear staining in malignant cells.


CONCLUSIONS
Cyclin D1 is amplified and overexpressed in ESCC and may be important in its molecular pathogenesis.
Nakagawa
H
H
Gastrointestinal Unit, Massachusetts General Hospital, Boston 02114, USA.
Zukerberg
L
L
Togawa
K
K
Meltzer
S J
SJ
Nishihara
T
T
Rustgi
A K
AK
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004938:Esophageal Neoplasms / Q000235:genetics*; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D016213:Cyclins; D017931:DNA Primers; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1