Article

[Expression of proline-rich tyrosine kinase-2 (Pyk2) in gastric carcinoma and its significance].

Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 07/2005; 37(3):261-4.
Source: PubMed

ABSTRACT To investigate whether proline-rich tyrosine kinase-2 (Pyk2) is expressed differently in normal gastric mucosas and gastric carcinoma tissues and further to evaluate its significance.
Expressions of Pyk2 in 59 cases of normal gastric mucosas and 52 cases of gastric carcinoma tissues were analysed by immunohistochemical methods.
Immunohistochemical studies showed that the positive rates of Pyk2 protein expression in normal gastric mucosas and gastric carcinoma tissues were 86.44% (51/59) and 19.23% (10/52) respectively. The difference between normal gastric mucosas and gastric carcinoma tissues was statistically significant (P<0.05). The positive rates of Pyk2 expression in highly differentiated gastric carcinoma and moderately/lowly differentiated gastric carcinoma were 47.37% (9/19) and 3.03% (1/33) respectively. Statistically significant differences (P<0.05) were observed in the levels of Pyk2 expression between highly differentiated gastric carcinoma and moderately/lowly differentiated gastric carcinoma. The positive rates of Pyk2 expression at different TNM stages gastric carcinoma were respectively: stage I 66.67% (6/9), stage II 30% (3/10), stage III 3.45% (1/29), stage IV 0% (0/4). The differences were statistically significant [(II+III+IV) v I, chi2=15.767, P<0.05].
In this study, we demonstrate that Pyk2 is expressed in normal gastric mucosas, whereas its expression declines significantly or almost disappears in gastric carcinoma tissues. The expression of Pyk2 progressively decreases with increasing grade of malignancy and TNM stages of gastric carcinoma. This phenomenon indicates that Pyk2 expression may be involved in the generation and development of gastric carcinoma.

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  • Article: Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness.
    Emy Behmoaram, Krikor Bijian, Su Jie, Yingjie Xu, Andrew Darnel, Tarek A Bismar, Moulay A Alaoui-Jamali
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    ABSTRACT: Early cancer cell migration and invasion of neighboring tissues are mediated by multiple events, including activation of focal adhesion signaling. Key regulators include the focal adhesion kinase (FAK) and FAK-related proline-rich tyrosine kinase 2 (Pyk2), whose distinct functions in cancer progression remain unclear. Here, we compared Pyk2 and FAK expression in breast cancer and their effects on ErbB-2-induced tumorigenesis and the potential therapeutic utility of targeting Pyk2 compared with FAK in preclinical models of breast cancer. Pyk2 is overexpressed in tissues from early and advanced breast cancers and overexpressed with both FAK and epidermal growth factor receptor-2 (ErbB-2) in a subset of breast cancer cases. Down-regulation of Pyk2 in ErbB-2-positive, FAK-proficient, and FAK-deficient cells reduced cell proliferation, which correlated with reduced mitogen-activated protein kinase (MAPK) activity. In contrast, Pyk2 silencing had little impact on cell migration and invasion. In vivo, Pyk2 down-regulation reduced primary tumor growth induced by a metastatic variant of ErbB-2-positive MDA 231 breast cancer cells but had little effect on lung metastases in contrast to FAK down-regulation. Dual reduction of Pyk2 and FAK expression resulted in strong inhibition of both primary tumor growth and lung metastases. Together, these data support the cooperative function of Pyk2 and FAK in breast cancer progression and suggest that dual inhibition of FAK and Pyk2 is an efficient therapeutic approach for targeting invasive breast cancer.
    American Journal Of Pathology 11/2008; 173(5):1540-50. · 4.89 Impact Factor
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Keywords

different TNM stages gastric carcinoma
 
differentiated gastric carcinoma
 
expression declines
 
Expressions
 
gastric carcinoma
 
gastric carcinoma tissues
 
immunohistochemical methods
 
Immunohistochemical studies
 
moderately/lowly differentiated gastric carcinoma
 
normal gastric mucosas
 
positive rates
 
proline-rich tyrosine kinase-2
 
Pyk2
 
Pyk2 expression
 
Pyk2 protein expression
 
stage IV 0%
 
Statistically significant differences
 
TNM stages
 

Hong-jie Guo