RGD Reference Report - The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma. - Rat Genome Database

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The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma.

Authors: Bahnassy, AA  Zekri, AR  Alam El-Din, HM  Aboubakr, AA  Kamel, K  El-Sabah, MT  Mokhtar, NM 
Citation: Bahnassy AA, etal., J Egypt Natl Canc Inst. 2006 Dec;18(4):292-302.
RGD ID: 2293574
Pubmed: PMID:18301453   (View Abstract at PubMed)

BACKGROUND: Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. METHODS: We investigated 110 subjects (43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CIN II, 18 CIN I) confirmed to be positive for HPV16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E, CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential PCR techniques. RESULTS: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16 (INK4A) (p=0.003, 0.001, 0.001) and a significant decrease in p27 (Kip1) from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27 (KIP1) and p16(INK4A) (p<0.001), cyclin D1 and CDK4 (p=0.001), cyclin E and p27 (Kip1) (p=0.011) in all studied groups. In ISCC, there was significant relationship between standard clinicopathological prognostic factors and high Ki-67 index , increased cyclin D1 and cyclin E, reduced p27 (Kip1) and p21 (waf). CONCLUSION: 1) Aberrations involving p27 (KIP1), cyclin E, CDK4 and p16 (INK4A) are considered early events in HPV 16 and 18-associated cervical carcinogenesis (CINI & II), whereas cyclin D1 aberrations are late events (CINIII & ISCC) 2) Immunohistochemical tests for p16 (INK4A) and cyclin E could help in early diagnosis of cervical carcinoma 3) Only FIGO stage, cyclin D1, p27 (Kip1) and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervix uteri carcinoma in situ  IEP 2293574; 2293574protein:increased expression:uterine cervixRGD 
cervix uteri carcinoma in situ disease_progressionIEP 2293574associated with Papillomavirus Infections and protein:increased expression:cervix epitheliumRGD 
cervix uteri carcinoma in situ disease_progressionIEP 2293574associated with Papillomavirus Infections and protein:decreased expression:cervical epitheliumRGD 
cervix uteri carcinoma in situ  ISOCCND1 (Homo sapiens)2293574; 2293574protein:increased expression:uterine cervixRGD 
cervix uteri carcinoma in situ  ISOCCNE1 (Homo sapiens)2293574; 2293574protein:increased expression:uterine cervixRGD 
cervix uteri carcinoma in situ disease_progressionISOCDK4 (Homo sapiens)2293574; 2293574associated with Papillomavirus Infections and protein:increased expression:cervix epitheliumRGD 
cervix uteri carcinoma in situ disease_progressionISOCDKN1B (Homo sapiens)2293574; 2293574associated with Papillomavirus Infections and protein:decreased expression:cervical epitheliumRGD 
Uterine Cervical Neoplasms disease_progressionIEP 2293574associated with Papillomavirus Infections and protein:increased expression:cervix epitheliumRGD 
Uterine Cervical Neoplasms disease_progressionIEP 2293574associated with Papillomavirus Infections and protein:decreased expression:cervical epitheliumRGD 
Uterine Cervical Neoplasms disease_progressionISOCDK4 (Homo sapiens)2293574; 2293574associated with Papillomavirus Infections and protein:increased expression:cervix epitheliumRGD 
Uterine Cervical Neoplasms disease_progressionISOCDKN1B (Homo sapiens)2293574; 2293574associated with Papillomavirus Infections and protein:decreased expression:cervical epitheliumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccnd1  (cyclin D1)
Ccne1  (cyclin E1)
Cdk4  (cyclin-dependent kinase 4)
Cdkn1b  (cyclin-dependent kinase inhibitor 1B)

Genes (Mus musculus)
Ccnd1  (cyclin D1)
Ccne1  (cyclin E1)
Cdk4  (cyclin dependent kinase 4)
Cdkn1b  (cyclin dependent kinase inhibitor 1B)

Genes (Homo sapiens)
CCND1  (cyclin D1)
CCNE1  (cyclin E1)
CDK4  (cyclin dependent kinase 4)
CDKN1B  (cyclin dependent kinase inhibitor 1B)


Additional Information