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Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.

Cho H, Noh KH, Chung JY, Takikita M, Chung EJ, Kim BW, Hewitt SM, Kim TW, Kim JH - PLoS ONE (2014)

Bottom Line: Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential.High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias.Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

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SCP3 overexpression is associated with tumor progression in human cervical neoplasia specimens.(A) Representative immunohistochemical staining images of SCP3 and pAKT in cervical tissue from patients with low-grade CIN, High-grade CIN, and cervical carcinoma. Boxed regions are displayed at high magnification in insets (scale bar: 300 µm). (B) Box plot depiction of IHC staining scores. There was an increasing amount of SCP3 and pAKT expression as tumor stage progressed from low-grade CIN to high-grade CIN to cancer. Symbols indicate individual samples. Numbers associated with symbols indicate case numbers.
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pone-0098712-g005: SCP3 overexpression is associated with tumor progression in human cervical neoplasia specimens.(A) Representative immunohistochemical staining images of SCP3 and pAKT in cervical tissue from patients with low-grade CIN, High-grade CIN, and cervical carcinoma. Boxed regions are displayed at high magnification in insets (scale bar: 300 µm). (B) Box plot depiction of IHC staining scores. There was an increasing amount of SCP3 and pAKT expression as tumor stage progressed from low-grade CIN to high-grade CIN to cancer. Symbols indicate individual samples. Numbers associated with symbols indicate case numbers.

Mentions: Representative immunohistochemical staining of SCP3 and pAKT are shown in Figure 5A. Immunohistochemical staining of SCP3 was observed in the cytoplasm of tumor cells as previously reported in non-small cell lung cancer [8]. The TMA constructed in this study consisted of 181 cases of cervical cancer, however due to the complexity of sectioning, staining, as well as heterogeneity of the samples, 176 (97.2%, SCP3) and 178 (98.3%, pAKT) of which were suitable for IHC evaluation. Detailed IHC scoring patterns are shown in Table S2. A total of 108 of 176 cancers (61.4%) had high expression (cut-off value: 7) of SCP3 whereas 100 of 178 cancers (56.2%) had elevated expression (cut-off value: 7) of pAKT. The level of SCP3 and pAKT expression increased as tumor state progressed from low-grade CIN to high-grade CIN to cancer (Figure 5A and 5B; Table S2). Moreover, SCP3 expression was significantly correlated with FIGO stage (P = 0.002), differentiation (P<0.001) and chemoradiation response (P = 0.005). However, there was no statistically significant difference between pAKT expression and clinicopathologic factors.


Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.

Cho H, Noh KH, Chung JY, Takikita M, Chung EJ, Kim BW, Hewitt SM, Kim TW, Kim JH - PLoS ONE (2014)

SCP3 overexpression is associated with tumor progression in human cervical neoplasia specimens.(A) Representative immunohistochemical staining images of SCP3 and pAKT in cervical tissue from patients with low-grade CIN, High-grade CIN, and cervical carcinoma. Boxed regions are displayed at high magnification in insets (scale bar: 300 µm). (B) Box plot depiction of IHC staining scores. There was an increasing amount of SCP3 and pAKT expression as tumor stage progressed from low-grade CIN to high-grade CIN to cancer. Symbols indicate individual samples. Numbers associated with symbols indicate case numbers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048308&req=5

pone-0098712-g005: SCP3 overexpression is associated with tumor progression in human cervical neoplasia specimens.(A) Representative immunohistochemical staining images of SCP3 and pAKT in cervical tissue from patients with low-grade CIN, High-grade CIN, and cervical carcinoma. Boxed regions are displayed at high magnification in insets (scale bar: 300 µm). (B) Box plot depiction of IHC staining scores. There was an increasing amount of SCP3 and pAKT expression as tumor stage progressed from low-grade CIN to high-grade CIN to cancer. Symbols indicate individual samples. Numbers associated with symbols indicate case numbers.
Mentions: Representative immunohistochemical staining of SCP3 and pAKT are shown in Figure 5A. Immunohistochemical staining of SCP3 was observed in the cytoplasm of tumor cells as previously reported in non-small cell lung cancer [8]. The TMA constructed in this study consisted of 181 cases of cervical cancer, however due to the complexity of sectioning, staining, as well as heterogeneity of the samples, 176 (97.2%, SCP3) and 178 (98.3%, pAKT) of which were suitable for IHC evaluation. Detailed IHC scoring patterns are shown in Table S2. A total of 108 of 176 cancers (61.4%) had high expression (cut-off value: 7) of SCP3 whereas 100 of 178 cancers (56.2%) had elevated expression (cut-off value: 7) of pAKT. The level of SCP3 and pAKT expression increased as tumor state progressed from low-grade CIN to high-grade CIN to cancer (Figure 5A and 5B; Table S2). Moreover, SCP3 expression was significantly correlated with FIGO stage (P = 0.002), differentiation (P<0.001) and chemoradiation response (P = 0.005). However, there was no statistically significant difference between pAKT expression and clinicopathologic factors.

Bottom Line: Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential.High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias.Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

Show MeSH
Related in: MedlinePlus