彭汪嘉康院士於4月30日(W一) 10:00-11:00 AM將邀請美國國家衛生院癌症研究中心遺傳學部主任Prof. Thomas Ried蒞臨誠樸廳演講，敬請各位老師踴躍出席並廣召學生、研究助理一同聆聽，感謝您的支持與協助。
時間: 2012年4月30日星期一 am:10:00-11:00
講者：Prof. Thomas Ried
講題：Exploiting the Cancer Genome and Transcriptome: Dissection of Molecular Pathways and Individualized Medicine
Genetic markers for disease progression of cervical dysplasia:
Aneuploidy and specific genomic imbalances are defining features in human carcinomas. For instance, invasive cervical carcinomas almost invariably carry extra copies of chromosome arm 3q, resulting in a gain of the human telomerase gene (TERC). We therefore decided to explore whether gain of 3q and genomic amplification of TERC can predict progression from low-grade lesions (CIN1 and CIN2) to high-grade lesions (CIN3) and invasive carcinoma. We applied FISH with a triple-color fluorescent probe set to previously stained Pap smears for which repeat Pap smears and clinical follow-up were available. We could show that the presence of 3q unequivocally predicted the progression risk of low-grade lesions and thus allows individualized treatment. These results were confirmed with histological diagnosis of biopsies.
Silencing of TCF7L2 sensitizes Wnt/β-catenin signaling-dependent colorectal cancer cells to radiation:
Aberrant canonical Wnt/β-catenin signaling plays a key role in colorectal tumorigenesis and tumor progression. We recently reported over-expression of TCF7L2 (TCF4), the binding partner of β-catenin and key transcription factor of canonical Wnt/β-catenin signaling, in rectal cancers that were resistant to preoperative chemoradiotherapy. Because therapy resistance represents a major clinical problem, we aimed to investigate the functional relevance of the observed over-expression of TCF7L2 for mediating radioresistance. We now show that RNAi-mediated silencing of TCF7L2 caused significant sensitization of colorectal cancer cell lines to clinically relevant doses of X-rays. This radiosensitization was the consequence of (i) a silencing-induced G2/M phase arrest, (ii) an impaired ability to adequately halt cell cycle progression after radiation, and (iii) a compromised DNA double strand break repair. Importantly, this radiosensitization was restricted to cell lines with high Wnt/β-catenin reporter activity. Thus, we have uncovered a novel role of Wnt/β-catenin signaling for mediating resistance to multimodal cancer therapy. Moreover, these data suggest that TCF7L2 is a promising molecular target to sensitize Wnt/β-catenin-dependent tumor cells to radiation. This has considerable clinical implications.
Keywords: Cervical cancer, aneuploidy, colorectal cancer, chemoradiotherapy, functional genomics