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M. Kawaguchi

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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-023 - The expression of ATBF1 is inversely proportion to the expression of estrogen receptor in lung cancer cells (ID 2668)

      09:30 - 16:30  |  Author(s): M. Kawaguchi

      • Abstract

      Sex difference is an important factor to differentiate the clinical characteristics of lung cancers. Sex hormones derived signaling should be involved in the etiology of lung cancers. The most important factor may be estrogen that is suspected carcinogen, since strong epidemiological evidence associates the hormone to breast, endometrial, and uterine cancers. We have been studied the involvement of ATBF1 that is a large transcription factor playing an important role as a tumor suppressor in various cancers. Intriguing fact is that estrogen at lower levels increases the expression of ATBF1, but at higher levels decreases ATBF1. The response of ATBF1 is explained by the negative feedback through the estrogen-responsive proteasome system. This is the first study to reveal the expression of ATBF1 in lung cancers and explain the clinical characteristic of lung cancer differentiated by sex.

      We prepared a cell line array from 17 lung cancer cell lines, which was consisted of twelve adenocarcinomas, three squamous cell carcinomas, one large cell carcinoma and one undifferentiated cancer. We generated five antibodies against ATBF1 (MB34-2, MB39-1, D1-120, MB44-2, MB47-2) at distinct part of the protein from N-terminal to C-terminal. We also analyzed the expression of p53, p21, ATM, psATM, estrogen receptors (ER), progesterone receptor (PR) , thyroid transcription factor 1 (TTF-1) and CEA by immunohistochemical analysis. The intensity of each factor was graded (score: 0-3) from weak expression (score: 0) to strong expression (score: 3). The intensity was scored in comparison with the intensity of ATB1 for other factors.

      Positive rates of ATBF1 with each antibody (MB34-2, MB39-1, D1-120, MB44-2, MB47-2) were 88%, 100%, 100%, 76% and 71%. Positive rates of p53, p21, ATM, psATM, ER, PR, TTF-1 and CEA were 53%, 41%, 47%, 41%, 65%, 42%, 29% and 76%, respectively. There was no significant difference in the expression pattern of each factor between adenocarcinoma and squamous cell carcinoma but TTF-1. We divided lung cancer cells into two groups by expression pattern of ATBF1. Wide range expression (W) group is characterized by the positive expression with all antibody whereas the limited expression (L) group that is characterized by limited number of positive with these antibodies. The expression rate of ER was significantly low in W group (45%, 5/11) in contrast to L group (100%, 6/6) (p=0.025).

      The higher expression of ER, the lower and limited expression of ATBF1. The observation may be relevant to the breaking down mechanism of ATBF1 through estrogen-ER signaling discovered in breast cancer. The protein stability of ATBF1 should be an important factor for the prognosis of lung cancer distinguished by the sex.