孕激素受体膜组分1在乳腺癌发生机制中作用的研究进展

摘要

Breast cancer is one of the most common leading cause of cancers death in women world-wide. But the mechanism of breast cancer development is still unclear. The only placebo-controlled study, the Women’s Health Initiative(WHI) demonstrated that breast cancer risk mainly is dependent on the progestogen component since only in the combined estrogen/progestogen arm, but not in the estrogen-only arm this risk was seen to increase the risk. According to this finding, our previous investigation point towards an important role of progesterone receptor membrane component 1 ( PGRMC1 ) in hormone related breast cancer risk. This finding got great attention from the related field in the world. An editorial published in the journal Menopause raised the following questions: “Can the increase in breast cancer observed in the estrogen plus progestin arm of the Women’ s Health Initiative trial be explained by progesterone receptor membrane component 1? Can the PGRMC1 become to be a potential marker in the future? Will the women with high expression of PGRMC1 be breast cancer susceptible people?” We will review the results of related researches.%乳腺癌是导致女性死亡的主要癌症之一,但目前为止关于乳腺癌的发生机制尚未完全明确。唯一一项全球大型安慰剂对照研究,妇女健康启动项目(Women’s Health Initiative,WHI)指出,雌孕激素联合治疗组乳腺癌风险增高,单一雌激素治疗组妇女的乳腺癌风险没有增加,反而有降低,说明在激素补充治疗( hormone replacement therapy,HRT)治疗中孕激素对乳腺癌风险具有负面影响。针对此结论开展了很多体外研究,发现雌孕激素联合治疗可以明显促进孕激素受体膜组分1( progesterone receptor membrane component 1,PGRMC1)表达阳性的乳腺癌细胞的增生。针对此结论,北美绝经学会官方科学杂志Menopause对此给予特别的编者按：“WHI研究中雌孕激素联合治疗组妇女乳腺癌风险增加是否可以用PGRMC1的作用来解释？ PGRMC1是否可以作为一个乳腺癌风险潜在的标志物？ PGRMC1高表达者是否可确定为乳腺癌易感者？”本文将就此方面的研究进行综述。