[Relationship of Stat3 and its target gene products with malignancy in human colorectal carcinoma].
OBJECTIVE
Signal transducers and activators of transcription 3 (Stat3) pathway can be activated by cytokines and growth factors, and activation of Stat3 is involved in modulating cell proliferation, differentiation, and apoptosis. Stat3 has been classified as an oncogene because Stat3 can mediate malignant transformation of cultured cells. This study was conducted to investigate the expression of Stat3 and its target gene products including Cyclin D1 and Bcl-x(L) in human colorectal carcinoma (CRC) tissues and cells, and to explore the mechanisms in tumorigenesis of CRC.


METHODS
The expression of Stat3, p-Stat3, Cyclin D1, and Bcl-x(L) in 45 cases of cancerous tissues, adjacent normal tissues, and two colon cancer cell lines including SW480 and HCT116 was measured by Western blot analysis. The expression pattern of Stat3 and its activated form p-Stat3 was determined by immunohistochemical staining. The relationship of the expression of p-Stat3, Cyclin D1, and Bcl-x(L) in CRC with various clinicopathological characteristics was analyzed statistically.


RESULTS
The protein expression rates of p-Stat3, Cyclin D1, and Bcl-x(L) in colorectal cancer and adjacent normal mucosa were 57.8%, 64.4%, 68.9%, and 42.2%, 35.6%, 31.1%,respectively; and their protein levels (A value) were 114263+/-53598, 58321+/-24872, 71032+/-43425 in colorectal cancer and 55971+/-28762, 22563+/-11160, 37281+/-14622 in adjacent normal mucosa (P< 0.05). Overexpression of p-Stat3 was correlated with clinical stage and nodal metastasis in colorectal cancer (P = 0.026 and P= 0.018, respectively). Elevated levels of Cyclin D1 were associated with nodal metastasis (P= 0.041). It was found that Cyclin D1 was in a positive linear correlation fashion with p-Stat3 in tumor (r = 0.382, P< 0.05). Activated Stat3 was also detected in both colon cancer cell lines SW480 and HCT116.


CONCLUSIONS
Stat3 signaling pathway may play an important role in the tumorigenesis of colorectal carcinoma. Determination of Stat3 and its target gene products can be used to indicate the malignancy degree of colorectal carcinoma.
Ma
Xiang-Tao
XT
Department of Surgery, Division of Surgical Oncology, People's Hospital, Peking University, Beijing, PR China.
Wang
Shan
S
Ye
Ying-Jiang
YJ
Du
Ru-Yu
RY
Cui
Zhi-Rong
ZR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D051020:bcl-X Protein; D019938:Cyclin D1