J Korean Cancer Assoc.  2000 Feb;32(1):110-119.

Expressions of Cell Cycle Control Genes in Human Uterine Cervical Cancer Cells

• Ahn JG
• Lee TS
• Cho JW
• Baek WK
• Suh SI
• Suh MH
• Park JW
• Cha SD

Abstract

PURPOSE: Recently, many aspects of biological functions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors and Rb gene have been reported, and the cell cycle control genes are considered to act important roles in tumorigenesis. In this study, the expression patterns of major cell cycle control genes (cyclin A, B, C, Dl, E, E2F, p16INK4a, p21WAF1 and Rb) in various human cervical cancer cells were analysed to elucidate the impacts of the cell cycle control genes on the carcinogenesis of human cervical cancer.
MATERIALS AND METHODS
The expression patterns of major cell cycle control genes in HT-3, C33-A, HeLa, C4-II, SiHa and CaSki human uterine cervical cancer cells were analysed by using western blot and reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
In most of the cervical cancer cells tested, the overexpressions of cyclin A, E, E2F and markedly decreased expression of Rb tumor suppressor proteins were observed. By comparing RNA and protein expressions in each cancer cells, the mechanisms of increased expressions of cyclin A, E and decreased expression of Rb were elucidated as post-translational controls.
CONCLUSION
The cervical carcinogenesis caused by the altered expressions of the major cell cycle control genes can be hypothesized as follows: overexpressions of cyclin E and A cause acceleration of Rb phosphorylations and E2F overexpression; increased E2F function accelerates G1/S transition of the cells; compensatory increase of p16 expression cannot stop the cells in Gl phase because Rb expression is severely decreased; consequently, loss of Rb function, 61 shortening, inappropriate cell division and decreased function of the maintenance of genomic stability occur. In addition to these alterations, loss of p53 functions further accelerate instability of genome and decrease the sus- ceptability to cell death. Furthermore, overexpression of Bc12 protects these abnormal cells from apoptosis. All these derangements of cell cycle control should contribute to the human cervical carcinogenesis.

Keyword

Cervix neoplasm; Tumor cell lines; Cell cycle control genes

MeSH Terms

Acceleration
Apoptosis
Blotting, Western
Carcinogenesis
Cell Cycle Checkpoints*
Cell Cycle*
Cell Death
Cell Division
Cell Line, Tumor
Cyclin A
Cyclin E
Cyclin-Dependent Kinases
Cyclins
Genes, Retinoblastoma
Genome
Genomic Instability
Humans*
Phosphorylation
RNA
Tumor Suppressor Proteins
Uterine Cervical Neoplasms*
Cyclin A
Cyclin E
Cyclin-Dependent Kinases
Cyclins
RNA
Tumor Suppressor Proteins