Objective To investigate the expression of hypoxia inducing factor 1 alpha (HIF-1α) in human breast cancer and its relationships with microvessel density （MVD）, proliferating cell nuclear antigen (PCNA) protein, other tumor biomarkers and clinicopathologic factors.
Methods Immunohistochemical staining (SP) was used to measure the expressions of HIF-1α and PCNA in human breast fibroadenoma, usual hyperplasia and adenocarcinoma, and the MVD was determined by anti-CD34 immunostaining.
Results No HIF-1α was observed in the lesions of breast fibroadenoma and hyperplasia. However, the positive expression rate of HIF-1α in the ductal carcinoma in situ （DCIS） was 55.0% (11/20) and the infiltrative breast cancer was 85.0%(51/60). The total high expression rate of PCNA in breast cancer was 75.0% (60/80), in which the rate of DCIS counted for 65.0% (13/20) and the rate of infiltrative adenocarcinoma counted for 78.3% (47/60). There were positive correlations between the expresson of HIF-1α and the expression of PCNA (r=0.693， P＜0.01) and MVD in DCIS (r=0.682, P＜0.05), respectively, but there was no relation between HIF-1α and MVD in infiltrative breast cancer. The expression of HIF-1α was associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status (P＜0.01).
Conclusion The expression of HIF-1α increased in breast cancer and it is associated with tumor cell proliferation, lymph node metastasis, estrogen receptor status. Thus, HIF-1α may play an important role in the tumor cell proliferation, vasiformation, progression and metastasis of breast cancer, and may become a new target for tumor treatment.
Citation：
HAO Langsong,ZHU Xia,QIAN Kun,ZHANG Qinghua,LUO Ting,LI Xiaojun,WANG Geng,WU Xiaoting. Expression of Hypoxia Inducing Factor 1 Alpha and Its Relationships with Proliferating Cell Nuclear Antigen and Microvessel Density in Human Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(2): 203-207. doi:
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- 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. 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. 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. 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. 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. 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. 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. 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. 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. Moeller BJ, Dreher MR, Rabbani ZN, et al. Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity [J]. Cancer Cell， 2005; 8(2)∶99.
