• 1.四川大學(xué)華西醫(yī)院普外科(成都610041);;
  • 2.鄖陽(yáng)醫(yī)學(xué)院附屬太和醫(yī)院外科(湖北十堰442000);

目的 　探討乳腺癌組織中缺氧誘導(dǎo)因子-1α（HIF-1α）的表達(dá)及其與增殖細(xì)胞核抗原（PCNA）、微血管密度（MVD）及臨床病理因素的關(guān)系。
方法 　采用免疫組化SP法檢測(cè)乳腺纖維腺瘤、普通乳腺增生組織和乳腺癌組織中HIF-1α及PCNA蛋白的表達(dá)，用CD34單克隆抗體標(biāo)記血管內(nèi)皮細(xì)胞并計(jì)數(shù)MVD。
結(jié)果 　HIF-1α蛋白在乳腺纖維腺瘤、普通乳腺增生組織中不表達(dá)； 在乳腺導(dǎo)管內(nèi)原位癌中表達(dá)陽(yáng)性率為55.0%（11/20），浸潤(rùn)性乳腺癌中為85.0%（51/60）； HIF-1α表達(dá)與淋巴結(jié)轉(zhuǎn)移及雌激素受體狀態(tài)有關(guān)(P＜0.01)。乳腺癌中PCNA高表達(dá)率為75.0%（60/80），其中導(dǎo)管內(nèi)原位癌中為65.0%（13/20），浸潤(rùn)性癌中為78.3%（47/60）。乳腺癌中HIF-1α表達(dá)與PCNA呈正相關(guān)（r=0.693，P＜0.01）,與導(dǎo)管內(nèi)原位癌中MVD亦呈正相關(guān)(r=0.682，P＜0.05)，與浸潤(rùn)性癌中MVD無(wú)相關(guān)關(guān)系。
結(jié)論 　HIF-1α在乳腺癌組織中的表達(dá)明顯上調(diào)，與腫瘤細(xì)胞增殖、血管形成、淋巴結(jié)轉(zhuǎn)移、雌激素受體狀態(tài)相關(guān)，提示HIF-1α對(duì)乳腺癌的腫瘤細(xì)胞增殖、血管形成、生長(zhǎng)和侵襲、轉(zhuǎn)移起重要作用，有望成為腫瘤治療的新靶點(diǎn)。

引用本文： 郝朗松,朱霞,錢昆,張清華,羅婷,李小軍,王耕,伍曉汀. 乳腺癌組織中缺氧誘導(dǎo)因子-1α的表達(dá)及其與增殖細(xì)胞核抗原、微血管密度的關(guān)系. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007, 14(2): 203-207. doi: 復(fù)制

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  2. 2. 　Acker T, Plate KH. A role for hypoxia and hypoxia-inducible transcription factors in tumor physiology [J]. J Mol Med， 2002; 80(9)∶562.
  3. 3. 　Bos R, van Diest PJ, van der Groep P, et al. Expression of hypoxia-inducible factor-1alpha and cell cycle proteins in invasive breast cancer are estrogen receptor related [J]. Breast Cancer Res， 2004; 6(4)∶R450.
  4. 4. 　Mommers EC, Poulin N, Meijer CJ, et al. Malignancy-associated changes in breast tissue detected by image cytometry [J]. Anal Cell Pathol， 2000; 20(4)∶187.
  5. 5. 　Akakura N, Kobayashi M, Horiuchi I, et al. Constitutive expression of hypoxia-inducible factor-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation [J]. Cancer Res， 2001; 61(17)∶6548.
  6. 6. 　Laughner E, Taghavi P, Chiles K, et al. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1 alpha (HIF-1 alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression [J]. Mol Cell Biol， 2001; 21(12)∶3995.
  7. 7. 　Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1 alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics [J]. Cancer Res， 2000; 60(6)∶1541.
  8. 8. 　Rose F, Grimminger F, Appel J, et al. Hypoxic pulmonary artery fibroblasts trigger proliferation of vascular smooth muscle cells: role of hypoxia-inducible transcription factors [J]. FASEB J， 2002; 16(12)∶1660.
  9. 9. 　Kung AL, Wang S, Klco JM, et al. Suppression of tumor growth through disruption of hypoxia-inducible transcription [J]. Nat Med， 2000; 6(12)∶1335.
  10. 10. 　Li L, Lin X, Staver M, et al. Evaluating hypoxia-inducible factor-1alpha as a cancer therapeutic target via inducible RNA interference in vivo [J]. Cancer Res， 2005; 65(16)∶7249.
  11. 11. 　Moeller BJ, Dreher MR, Rabbani ZN, et al. Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity [J]. Cancer Cell， 2005; 8(2)∶99.