TY - JOUR
T1 - Positive association between nuclear Runx2 and oestrogen-progesterone receptor gene expression characterises a biological subtype of breast cancer
AU - Das, Kakoli
AU - Leong, David Tai
AU - Gupta, Anurag
AU - Shen, Liang
AU - Putti, Thomas
AU - Stein, Gary S.
AU - van Wijnen, Andre J.
AU - Salto-Tellez, Manuel
N1 - Funding Information:
We would like to thank Dr. Doris Mayer, German Cancer Research Center, Germany for the kind gift of ER expression plasmid. Our study was supported by SCS Grants MN05 and MN077 (to MST), NIH Grants P01CA82834 (to G.S.S.) and AR049069 (to AJvW.) and NUS ARF R-364-000-089-112 (to DTL).
PY - 2009/9
Y1 - 2009/9
N2 - Purpose: The runt-related transcription factor, Runx2 may have an oncogenic role in mediating metastatic events in breast cancer, but whether Runx2 has a role in the early phases of breast cancer development is not clear. We examined the expression of Runx2 and its relationship with oestrogen receptor (ER) and progesterone receptor (PR) in breast cancer cell lines and tissues. Methods: Two human breast cancer cell lines, MCF-7 and MDA-MB-231 were transiently transfected with vectors expressing either Runx2 or ER and the levels of both proteins and mRNA were examined by Western blot analysis and quantitative real-time PCR, respectively. Runx2 expression was also examined in tissue microarray sections of 123 breast cancer patients by immunohistochemistry and results were correlated with clinico-pathological characteristics. Results: Expression of Runx2 and ER was reciprocal in the breast cell culture models and Runx2 suppressed ERβ but not ERα mRNA levels. In contrast, functional expression of Runx2 was evident in the nucleus in 28% of the breast cancer tissues and in both early and late stages of tumour growth. Importantly, Runx2 expression was significantly more frequent in Grade 2 compared to Grade 1 and Grade 3 tumours (48% versus 39% versus 13%) and the expression was significantly associated with ER (p = 0.005), PR (p = 0.008) expressions in Grade 2 & Grade 3 tumours than Grade 1 tumours. Conclusion: We propose that Runx2, ER and PR triple positivity in Grades 2 and 3 defines a biological subtype in breast cancer.
AB - Purpose: The runt-related transcription factor, Runx2 may have an oncogenic role in mediating metastatic events in breast cancer, but whether Runx2 has a role in the early phases of breast cancer development is not clear. We examined the expression of Runx2 and its relationship with oestrogen receptor (ER) and progesterone receptor (PR) in breast cancer cell lines and tissues. Methods: Two human breast cancer cell lines, MCF-7 and MDA-MB-231 were transiently transfected with vectors expressing either Runx2 or ER and the levels of both proteins and mRNA were examined by Western blot analysis and quantitative real-time PCR, respectively. Runx2 expression was also examined in tissue microarray sections of 123 breast cancer patients by immunohistochemistry and results were correlated with clinico-pathological characteristics. Results: Expression of Runx2 and ER was reciprocal in the breast cell culture models and Runx2 suppressed ERβ but not ERα mRNA levels. In contrast, functional expression of Runx2 was evident in the nucleus in 28% of the breast cancer tissues and in both early and late stages of tumour growth. Importantly, Runx2 expression was significantly more frequent in Grade 2 compared to Grade 1 and Grade 3 tumours (48% versus 39% versus 13%) and the expression was significantly associated with ER (p = 0.005), PR (p = 0.008) expressions in Grade 2 & Grade 3 tumours than Grade 1 tumours. Conclusion: We propose that Runx2, ER and PR triple positivity in Grades 2 and 3 defines a biological subtype in breast cancer.
KW - Breast cancer
KW - CerbB2
KW - Oestrogen receptor
KW - Progesterone receptor
KW - Runx2
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U2 - 10.1016/j.ejca.2009.06.021
DO - 10.1016/j.ejca.2009.06.021
M3 - Article
C2 - 19632824
AN - SCOPUS:68749118305
SN - 0959-8049
VL - 45
SP - 2239
EP - 2248
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 13
ER -