TY - JOUR
T1 - Senescence and apoptosis in carcinogenesis of cervical squamous carcinoma
AU - Feng, Wei
AU - Xiao, Jianguo
AU - Zhang, Zhihong
AU - Rosen, Daniel G.
AU - Brown, Robert E.
AU - Liu, Jinsong
AU - Duan, Xiuzhen
PY - 2007/9
Y1 - 2007/9
N2 - Senescence and apoptosis are two key mechanisms that protect against cancer development. Many cell cycle regulators, such as p14ARF, p15 INK4b and p16INK4a, are important in G1 cell cycle arrest and oncogene-induced senescence. The bcl-2 protein is one of the key components that control apoptosis, while the p53 protein plays key roles in both mechanisms. The genes of these key regulator proteins are often mutated or deleted in various malignancies. It is unknown how senescence and apoptosis are regulated in one of the most common tumors of the female genital tract, cervical squamous cell carcinoma (SCC). In this study the, expression of senescence, apoptosis and proliferation markers in normal cervical epithelium, cervical intraepithelial neoplasia (CIN) and SCC are characterized via immunohistochemical staining for p14ARF, p15INK4b, p16INK4a, bcl-2, p53 and Ki-67 in tissue microarray blocks containing 20 samples each of normal cervix, moderate-to-severe cervical dysplasia (CIN II-III) and invasive SCC. Samples are derived from 60 total cases of cervical biopsies and cervical conizations. Results showed that the proliferation marker, Ki-67, is markedly increased, and the senescence markers, p15INK4b, p16INK4a and p14ARF are overexpressed in both dysplasia and carcinoma. P53 immunostain is negative in all normal cervical tissue, and positive in dysplasia and carcinoma. Although the expression of bcl-2 is increased in dysplasia, this marker is negative in approximately half of SCC cases. These results suggest that some senescence pathways are activated and are still maintained in cervical dysplasia and carcinoma. However proliferation is increased and carcinogenesis is not thwarted, leading to eventual development of cervical cancer. Other mechanisms, such as those that account for the apparent overexpression of p53 and paradoxical loss of bcl-2 expression in some SCC cases, as well as additional senescence and apoptotic pathways, may play key roles carcinogenesis of cervical SCC.
AB - Senescence and apoptosis are two key mechanisms that protect against cancer development. Many cell cycle regulators, such as p14ARF, p15 INK4b and p16INK4a, are important in G1 cell cycle arrest and oncogene-induced senescence. The bcl-2 protein is one of the key components that control apoptosis, while the p53 protein plays key roles in both mechanisms. The genes of these key regulator proteins are often mutated or deleted in various malignancies. It is unknown how senescence and apoptosis are regulated in one of the most common tumors of the female genital tract, cervical squamous cell carcinoma (SCC). In this study the, expression of senescence, apoptosis and proliferation markers in normal cervical epithelium, cervical intraepithelial neoplasia (CIN) and SCC are characterized via immunohistochemical staining for p14ARF, p15INK4b, p16INK4a, bcl-2, p53 and Ki-67 in tissue microarray blocks containing 20 samples each of normal cervix, moderate-to-severe cervical dysplasia (CIN II-III) and invasive SCC. Samples are derived from 60 total cases of cervical biopsies and cervical conizations. Results showed that the proliferation marker, Ki-67, is markedly increased, and the senescence markers, p15INK4b, p16INK4a and p14ARF are overexpressed in both dysplasia and carcinoma. P53 immunostain is negative in all normal cervical tissue, and positive in dysplasia and carcinoma. Although the expression of bcl-2 is increased in dysplasia, this marker is negative in approximately half of SCC cases. These results suggest that some senescence pathways are activated and are still maintained in cervical dysplasia and carcinoma. However proliferation is increased and carcinogenesis is not thwarted, leading to eventual development of cervical cancer. Other mechanisms, such as those that account for the apparent overexpression of p53 and paradoxical loss of bcl-2 expression in some SCC cases, as well as additional senescence and apoptotic pathways, may play key roles carcinogenesis of cervical SCC.
KW - Apoptosis
KW - Carcinogenesis
KW - Carcinoma
KW - Cervical squamous
KW - Senescence
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U2 - 10.1038/modpathol.3800927
DO - 10.1038/modpathol.3800927
M3 - Article
C2 - 17632454
AN - SCOPUS:34547955181
SN - 0893-3952
VL - 20
SP - 961
EP - 966
JO - Modern Pathology
JF - Modern Pathology
IS - 9
ER -