Smad4 deficiency in cervical carcinoma cells

     Speaker: 余婧萱                     Time: 15:00~16:00  04/27/2005

     Commentator: 劉校生 老師            Place: 601

Abstract:

Squamous cell carcinoma of the uterine cervix is one of the most frequent cancers affecting women worldwide. The carcinomas arise from cervical intraepithelial neoplasia (CIN) lesions and infection with human papillomavirus (HPV) is a crucial step in the etiology of cervical carcinoma. The molecular mechanisms underlying progression to invasive tumor growth are poorly understood. Since Smad4 plays a central transmitter of TGF-β responses, then the authors analyzed the Smad4 expression status in 13 cervical cancer cells, and four of them were functional inactivation. Compared with the cervical cancer cells, CIN lesions and primary squamous cervical carcinomas were used in this study, 10 out of 41 cases of squamous cell carcinoma exhibited Smad4 loss, whereas all normal epithelia and CIN lesions showed moderate or strong Smad4 expression. Unfortunately, the Smad4 status didn’t correlate with TGF-β responsiveness; even Smad4 was an important transmitter in the TGF-β signaling pathway. Moreover, the inactivation of Smad4 in four cervical cancer cells were not concerned with the integration of HPV viral DNA, even close to the location of Smad4. According to the expression among 81 clinical samples of CIN lesions and primary squamous cervical carcinomas, Smad4 lost its expression in the invasive carcinomas but not in the CIN lesions, the authors suggested that loss of Smad4 activity may play a significant role in cervical carcinogenesis.

References:

1.  Peter ten Dijke and Caroline S. Hill  New insights into TGF-β–Smad signaling.  TRENDS Biochem. Sci. 29, 265-273(2004)

2.  Rebecca L., et al  Role of transforming growth factor beta in human cancer.  J. Clin. Oncol. 23, 2078-2093(2005)