Expression of Cell Cycle–Regulated Proteins pRB2/p130, p107, E2F4, p27, and pCNA in Salivary Gland Tumors: Prognostic and Diagnostic Implications

Russo, Giuseppe; Zamparelli, Alessandra; Howard, Candace M.; Minimo, Corrado; Bellan, Cristiana; Carillo, Giovanna; Califano, Luigi; Leoncini, Lorenzo; Giordano, Antonio; Claudio, Pier Paolo

doi:10.1158/1078-0432.ccr-04-2508

Cited by 33 publications

(22 citation statements)

References 46 publications

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“…PCNA, an auxiliary protein for DNA polymerase ‰, plays an important role in DNA synthesis and is thought to be localized to nuclei, particularly during late G and S phases (31,32). The expression of PCNA is a useful marker in evaluating the cell proliferating activity in human salivary gland tumors (33,34). In this study, Bub1 protein expression correlated with PCNA expression using Western blot analysis.…”

Section: Discussionmentioning

confidence: 71%

Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

Shigeishi

Yoneda²,

Taki³

et al. 2006

Oncol Rep

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Abstract. Human Bub1 plays an important role at the spindle assembly check-point to prevent cell cycle progression following spindle damage. We examined the expression of Bub1 mRNA and protein in 21 human salivary gland tumors (7 pleomorphic adenomas, 2 warthin tumors, 5 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas and 4 acinic cell carcinomas) and 3 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) or Western blotting. The mean expression levels of Bub1 mRNA and protein were higher in malignant tumors (0.12±0.028/1.75±0.53) than normal submandibular glands (0.042±0.014/0.19±0.044) and benign tumors (0.058±0.01/0.97±0.44). We found a significant association between the level of Bub1 mRNA/protein expression and clinical stage in malignant tumors (Mann-Whitney U test, p=0.019/p=0.016). We analyzed its relation with the proliferative activity monitored by the Ki-67 labeling index by immunohistochemistry as well as the expression of proliferating cell nuclear antigen (PCNA) by Western blotting. A significant correlation was found between Bub1 mRNA/ protein expression and the Ki-67 labeling index in salivary gland tumors (Spearman's correlation coefficient by rank test, p=0.026/p=0.002). These results indicate that increased expression of the human Bub1 gene is closely linked to abnormal cell proliferation in malignant conditions.

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Section: Discussionmentioning

confidence: 71%

Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

Shigeishi

Yoneda²,

Taki³

et al. 2006

Oncol Rep

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“…Interestingly, p107 nuclear expression showed a strong direct correlation when compared with the same variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels in the specimens examined and the tightest inverse correlation (Po0.0001) with both histological grading and PCNA expression in malignant salivary tumors (Russo et al, 2005).…”

Section: Head and Neck Cancermentioning

confidence: 87%

RB family members as predictive and prognostic factors in human cancer

2006

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“…Sequences were compared with the GenBank database as described by Levi et al 18 Immunohistochemistry. IHC was performed as described previously by Russo et al 19 For the primary tumors, the test was done on 4 µm sections mounted on positively charged slides. In the case of Ki-67, the antigen retrieval was done using protease treatment.…”

Section: Methodsmentioning

confidence: 99%

The effects of HIV-1 Tat protein on cell cycle during cervical carcinogenesis

Nyagol¹,

Leucci²,

Onnis³

et al. 2006

Cancer Biology & Therapy

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The role of HPV in the carcinogenesis of intraepithelial and invasive anogenital lesions is currently well established. E6 and E7 oncoproteins of high-risk HPV genotypes are known to inactivate p53 and pRb pathways. Several studies have described an increased prevalence and recurrence of both cervical HPV infection and invasive cervical cancer among HIV-1 positive women compared to HIV-1 negative cases. For these reasons, cervical cancer is considered an AIDS-defining neoplasm. Unlike other AIDS-associated neoplasms, the occurrence of cervical cancer is independent of immune suppression. HIV-1 infection in patients with high grade precancerous lesions and invasive cervical cancers results in a therapy refractory and more aggressive disease phenotype, which is not yet well understood at the molecular level. An upregulation of HPV E6 and E7 gene expressions by HIV-1 proteins such as Tat has been documented by some authors. However, the role of HIV-1 in cervical carcinomas is still unclear. It is already known that HIV-1 Tat protein is able to influence cell cycle progression. Altogether, these facts led us to investigate the effects of Tat on the expression of cell cycle regulator genes. After transfection of HeLa cells with Tat, we analyzed the expression of cell cycle regulators from these cells by IHC and Real-time PCR. A significant reduction in the expression of cell cycle inhibitors of transcription and an increase in the levels of proliferation markers were observed. These results suggest that HIV-1 may enhance cervical carcinogenesis by promoting cell cycle progression. We also found that this HIV-1 Tat-induced cell proliferation was not dependent on the E2F family of transcription factors, and therefore postulate that Sp factors may be involved.

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Expression of Cell Cycle–Regulated Proteins pRB2/p130, p107, E2F4, p27, and pCNA in Salivary Gland Tumors: Prognostic and Diagnostic Implications

Cited by 33 publications

References 46 publications

Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

RB family members as predictive and prognostic factors in human cancer

The effects of HIV-1 Tat protein on cell cycle during cervical carcinogenesis

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