Study links normal stem cells to aggressive prostate cancer
Researchers identify potential new treatment options for therapy-resistant prostate cancer
MD Anderson News Release February 29, 2016
A study that revealed new findings about prostate cells may point to future strategies for treating aggressive and therapy-resistant forms of prostate cancer.
The study proved that the prostate basal cell layer contains adult stem cells which possess a unique gene expression profile resembling the deadliest form of prostate cancer. The research was led byThe University of Texas MD Anderson Cancer Center与发表在2月29日网上发行结果Nature Communications.
“它已经成为为人类前列腺癌是否包含成人干细胞或不和他们所在的基底或管腔细胞小室中很有争议的，”说Dean Tang, M.D., Ph.D.,教授表观遗传学和分子致癌作用。“我们的研究提供了确切的证据表明，前列腺基底细胞层港口是在干细胞基因的丰富自我更新的成体干细胞。”
Tang and his team headed by Dingxiao Zhang, Ph.D., an instructor in Tang’s lab, show that the findings point to a “theoretical rationale for combining Pol-I and MYC inhibitors to treat highly aggressive forms of prostate cancer which are resistant to endocrine therapy.” Pol-I is an enzyme involved with DNA replication and MYC is a regulator gene that plays a role in cell death and transformation.
前列腺包含基底和管腔细胞，两者都被认定为“细胞的原产地”为前列腺癌在最近的小鼠研究。然而，无论是在哪里干细胞的问题存在于人类前列腺已基本医疗神秘和恒定的辩论到现在。
唐的球队完成使用RNA测序人类良性前列腺基底和管腔细胞的全基因组分析，发现这些差异表达基因，一些基底细胞代表自我更新的成体干细胞。
“Strikingly, we found that basal stem cells also expressed a large cohort of ‘proneural’ genes that are normally involved in regulating the nervous system development,” said Tang. “These proneural genes seem to play important functions in conferring stem cell-like properties upon some basal cells.”
This finding is important because a subset of prostate cancers (less than 5 percent) are highly aggressive and do not respond to current anti-prostate cancer treatments such as endocrine therapy.
“奇怪的是，这些难以治疗的癌症也表达的基因签名重叠我们正常的基底干细胞基因表达图谱，表明基底干细胞可能代表这些前列腺癌的细胞的原产地，”唐说。“具有重要意义的，基底干细胞基因表达图谱也与内分泌治疗抗性癌是致死几乎所有的晚期前列腺癌患者。”
唐的研究小组还发现，基底干细胞在部分被MYC其报价希望致命前列腺癌和治疗抗性前列腺癌的可能有新的治疗选择调控的遗传成分丰富。
“我们的研究证明疗法，结合POL-1和Myc抑制剂可能是治疗的高转移和内分泌治疗抵抗性前列腺癌的潜在的新线，”唐说。
MD Anderson study team members included Yi Zhong, Ph.D., Yue Li, Ph.D., Kiera Rycaj, Ph.D., Shuai Gong, M.D., Ph.D., Xin Chen, Ph.D., Xin Liu, Ph.D., Hsueh-Ping Chao, Ph.D., Pamela Whitney, Tammy Calhoun-Davis, Yoko Takata, and Jianjun Shen, Ph.D., all of Epigenetics and Molecular Carcinogenesis.
Other participating institutions included The University of Texas at Austin, and Tongji University School of Medicine, Shanghai.
这项研究是由美国国立卫生研究院（RO1-CA155693和R01-CA95548）的资助，国防部（W81XWH-13-1-0352和W81XWH-14-1-0575）部和得克萨斯州癌症预防和研究所188bet体育网址（RP120194）。