| Summary: | 碩士 === 臺北醫學大學 === 醫學研究所 === 92 === Abstract
Epidermiological reports on the role of smoking in breast carcinogenesis are controversial. However, evidences indicate that rapid serine/threonine kinase Akt (Protein kinase B) activation play an important role of carcinogenesis, such pathway were induced by nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-
1-butanone (NNK) in lung epithelial cell and also by estradiol in breast cell. It provides the idea that nicotine and NNK exposure may activates Akt , resulting of cell proliferation in breast cell. Our objective of study is to evaluate the nicotinic acetylcholine receptors (nAchRs) expression in breast cancer tissues of Taiwanese female patients, and the relation of clinicopathologic features between such receptors expression is analyzed. We obtained human breast specimens from 18 patients with invasive ductal carcinoma and 2 patients with ductal carcinoma in situ. cDNA of nAchRs were studied by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) in breast cancer specimens, normal breast tissue adjacent to the cancer and human breast cancer cell lines. α9-containing andα10-containing nAchRs were expressed in 19 and 11 of 20 breast cancer samples; they were also expressed in 18 and 9 of 20 normal breast samples adjacent to the cancer, respectively. Expression of other subunits of nAchR are not frequent. Compare with the intensity of nAchR band, most specimens showed significant expression of α9 and α10 subunits in breast cancer tissue relative to the corresponding normal tissue. Besides, there was a significant association between α9- containing andα10-containing nAchRs synchronous expression in both cancer and normal tissues with local tumor extent (P=0.009). Multivariate general linear model showed thatα10-containing nAchR expression in breast tumor cells is the most importart factor of tumor size among the other subunits. In breast cancer cell line MCF-7, α1, α3, α5, α7, α9, α10 andβ4-containing nAchRs were expressed, whereas onlyα5 andα9 subunits expression in MDA-MB-231 cell. Our data support the hypothesis that nicotine and NNK may contribute to the initiation and progression of human breast cancer, further in vitro and in vivo studies to confirm such hypothesis is required.
Key words: nAchRs, nicotine, NNK, tobacco-related carcinogen, estradiol, Akt, MCF-7, MDA-MB-231, invasive ductal carcinoma, ductal carcinoma in situ
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