[雙語翻譯]--醫(yī)學(xué)外文翻譯--人賁門癌癌變進(jìn)程中c-src基因的表達(dá)（原文）

1、The expression of c-src gene in the carcinogenesis process of human cardia adenocarcinomaWANG Xiu-Jia, YUAN Shu-Lan, XIAO Lin, WANG Xu-Hua and WANG Chao-JunPO Box 2345, Beijing 100023, ChinaWJG, 1999 December; 5(6):488-4

2、91 Fax: +86-10-85381893World Journal of Gastroenterology E-mail: wjg@wjgnet.com www.wjgnet.comCopyright?1999 by the WJG Press ISSN 1007-9327Subject headings c-src gene; expression product; PP60c-src;

3、 cardia adenocarcinoma; carcinogenesis; neoplasm metastasis; immunohi stochemistryAbstractAIM To investigate the activation, expression of c-src gene and its role in the carcinogenetic process of h

4、uman cardia adenocarcinoma (CA). METHODS Fifty-six cases of CA, 34 cases of normal, 36 cases of protife rative epithelia adjacent to carcinoma, and 20 cases of lymph node metastases of CA were studied for PP60c-src

5、, the expression product of c-src gene immunohistochemically by using the specific monoclonal antibody, Mab327. RESULTS The positive rates of PP60c-src in the normal ep ithelia, protiferative epithelia, CA and lymph node

6、 metastases were 29.4% (10/ 34), 94.4% (34/36), 71.4% (40/56) and 60.0% (12/20), respectively, among them, the differences of the positive rates were statistically significant ( P < 0.01 ). The expression l

7、evels of PP60c-src in CA and proliferative epithe lia were significantly higher than that in the normal epithelia (P<0.01) . The PP60c-src positive rates in the papillary, tubular, poorly differentiated and

8、mucous adenocarcinoma were 75.0% (6/8), 81.8% (18/22), 50.0% (10/20) and 100.0% (6/6), respectively, whereas those of tubular and mucous adenocarcinomas were significantly higher than those of papillary and poorly differ

9、entiated adenocarcinomas (P<0.05), and the PP60c-src expression levels of tubular andmucous adenocarcinomas were also significantly higher than those of papillary and poorly differentiated adenocarci nomas(P<0.01).

10、 CONCLUSION The activation and expression of c-src gene are associated with the initiation and development of human CA; the protein amount of PP60c-src increased during the process of carcinogenesis; and PP60c-src expres

11、sion is also related to lymph node metastases.INTRODUCTION There is a general tendency in gastric cancer that the incidence rate of cardia adenocarcinoma (CA) is increasing steadly, and cancer of the

12、 distal stomach is decreasing proportionately. The biological and epidemiological features of CA are distinct from those of the distal stomach, and the underlying cause remained unelucidated[1-3]. P

13、P60c-src is the product of c-src gene pos sessing the activity of tyrosine kinase. Increased expression ofc-src gene had been reported in some human sarcoma and cancers of breast[4], esoph agus[

14、5], stomach[6] and colon[7], and the activation and expression of c-src gene might be associated with the initiation and devel opment of some cancers. Our previous study showed the activation an

15、d expression of c-src gene was associated with the development and differentiation of esophageal squamous cell carcinomas[8], we believed that s imilar changes might occur in cancer of cardia,

16、 therefore, the following study was carried out.MATERIALS AND METHODSSample collection and processing All 56 cases of CA samples were collected from the CA patients surgically treated in Yanting

17、Institute of Cancer Prevention of Sichuan Province. All tissue specimens were routinely processed, formalin- fixed and paraffin-embedded, at least 2 serial paraffin sections of 4 µm - 6

18、µm thickness were made, one was stained with hematoxylin and eosin (HE) and the other was use d for PP60c-src protein detection by immunohistochemical staining.Reagents The monoclonal antibody

19、 Mab327 (mouse IgG) was kindly given by the Molecular PathologyInstitute of Cancer Research, Cancer Center, The First University Hospital of West China University of Medical Sciences, Chengdu 610041, Sic

20、huan Pro vince, China WANG Xiu-Jie, male, born on 1957-02-15 in Ziyang, Sichuan Province and graduated from West China University of Medical Sciences in 1982, now Associat e Professor of Oncology, engaged in the research

21、es of etiology and mechanisms of carcinogenesis of cancers, screening and developing anti-cancer drugs, having 20 papers published. Project supported by the grant of West China University of Medical Scien ces, No.L2930

22、15 Correspondence to: WANG Xiu-Jie, Institute of Cancer Research, Cancer Center, The First University Hospital of West China University of Medical Sciences, Chengdu 610041, Sichuan Province, China. Tel. +86·28·

23、;5501218, Fax. +86·28·5583252 Received 1999-07-21 Accepted 1999-09-22Figure 1 The expression of PP60c-src in the p roliferative epithelia adjacent to carcinoma. LSAB×200 Figure 2 The expression of PP60c

24、-src in tubular adenocarcinoma. LSAB×200 Figure 3 The expression of PP60c-src in the poorly differentiated adenocarcinoma. LSAB×200 Figure 4 The expression of PP60c-src in the lymph node metastasis of CA. LSAB&

25、#215;200Table 1 The expression of PP60c-src in CA and related lesionsStaining intensity LesionCasePositive rate-(%) +(%) + +-+ + +(%) (%)Normal epithelia 34 24(70.5) 10(29.4) 0(0)10(29.4) Proliferativ

26、e epithelia 36 2 (5.6) 6(16.7) 28(77.8)d 34(94.4)bCardia adenocarcinoma 56 16(28.6) 20(35.7) 20(35.7)d 40(71.4)bLymph node metastases 20 8(40.0) 8(40.0) 4(20.0) 12(60.0)bP<0.01, in comparison of

27、 the positive rates in different lesions (χ2=34.19) vs normal epithelia; dP<0.01, in comparison of the positive intensity in different lesions ( χ2 = 25.08) vs normal epithelia.Table 2 The expression of PP60c-src

28、 in CA of different histo logical typesStaining intensity LesionCasePositive rate-(0/10) +(%) + +-+ + +(%) (%)Papillary8 2(25.0) 6(75.0) 0(0)6(75.0) Tubular 22 4(18.2)

29、 4(18.2) 14(63.6)b 18(81.8)aPoorly differentiated 20 10(50.0) 10(50.0) 0(0)10(50.0) Mucous 6 0(0) 0(0) 6(100.0)b 6(100.0)aTotal56 16(28.6) 20(35.7) 20(35.7)

30、 40(71.4)aP<0.05,in comparison of the positive rat es of tubular and mucous adenocarcinomas vs those of papillary and poorly differentiated adenocarcinomas (χ2 = 8.11); bP<0.01,in comparison of the positive rates

31、 of tubular and mucous adenocarcinomas vs those of papillary and poorly differentiated adenocarcinomas (χ2 = 27.56).DISCUSSION PP60c-src is a phosphorylated cytoplasmic protein encoded by c-src gene, having the

32、 activity of tyrosine kinase. The expression of PP60c-src can be found in many normal cells, which plays important roles in the regulation of cell proliferation, differentiation and transforma

33、tion[4] Recent studies indicated that the increase in the amount of PP60c-src protein and kinase activity was associated with initiation and development of some human neoplasms, and the activati

34、on and increase of expression were one of the factors for cancer initiation[4-8]. In this study, the expressions of PP60c-src in CA, proliferative epithelia and normal epithelia were 71.4% ( 4

35、0/56 ), 94.4% ( 34/36 ) and 29.4% (10/34), respectively and the positive rates of PP60 c-src in CA and proliferative epithelia were much higher than that in the normal epithelia (P<0.01). J

36、ankowiski et al analyzed the expression product of c-src gene in 15 cases of esophageal adenocarcinoma and 15 cases of Barrett’s esophageal epithelia immunohistochemically, the positive rates we

37、re 20% (3/15), suggestin that the expression of c-src gene is related to the development of esophageal adenocarcinoma. Therefore, the results of t his study indicated that the activation a

38、nd expression of c-src gene might be associated with the initiation and development of CA. However, the high expre ssion of PP60c-src in the proliferative epithelia might be associated with the

39、 proliferation of glandular epithelial cells, occurring in the aged rats[9]. The low PP60c-srcexpression in some normal epithelia adjacent to cancer might be explained by the fact that there