Estrogen(雌性荷爾蒙)已知與許多組織的生長、發育相關。而這些作用係透過Estrogen receptor (ER)來達成。ER是一個Nuclear transcription factor；當Estrogen與其結合時，會誘發一連串反應，進而活化或抑制Target genes的表達。固然，Estrogen刺激所產生的生理反應與ER被活化成Transcription factor有相當大的關係；但也不能排除其他Signaling pathways因受Estrogen刺激活化、參與其間而有以致之。惟Estrogen如何活化Signaling pathways目前仍不是很清楚。但先前已有報導指出Estrogen刺激所造成DNA的合成會因Tyrosine kinase inhibitors的存在而降低；且Estrogen刺激後細胞內蛋白的Tyrosyl phosphorylation也會顯著增加。目前已有報導指出Estrogen刺激會提高c-Src活性、強化Shc phosphorylation、活化Ras/MAPK。但相較於c-Src，另一個重要的Tyrosine kinase-focal adhesion kinase (FAK)其是否受Estrogen刺激而變化則鮮少有報導。在探討Estrogen訊息傳遞的過程中，我們意外發現Estrogen會刺激FAK表達量的增加。為進一步探討此一現象，我們設計Mammalian DNA expression constructs來了解FAK在Estrogen-induced signaling中可能扮演的角色。
Estrogen is known to participate in growth and development in various tissues. And all these cellular functions are mediated through estrogen receptor (ER) that is a nuclear transcription factor. Estrogen binding to the ER triggers a series of molecular events culminating in the activation or repression of target genes. All the physiological functions of estrogen can be attributed to the activated ER that acts as a transcription factor as well as the signaling pathsways that are induced or activated by estrogen. However, to date, the effects of estrogen on cellular signaling pathways are still unclear. Previously, it was demonstrated that tyrosine kinase inhibitors could block estrogen-induced mitogenesis. And upon estrogen stimulation, enhanced tyrosyl phosphorylation of total cellular proteins was detected. There were reports indicating the activiation of c-Src enzymatic activity, the enhancement of tyrosyl phopsphorylation of Shc and the activation of Ras/MAPK in response to estrogen. However, what happened to the other important tyrosine kinase, FAK, was still obscure. In the process of investigating the signaling pathways induced by estrogen, we unexpectedly observed that FAK was induced after estrogen treatment. To further study the phenomenon and its implicated significance, we are interested to design mammalian DNA expression constructs and generate cells overexpressing FAK to investigate the participation of FAK in estrogen-induced signaling.
