Apoptosis and tumor inhibition induced by human chorionic gonadotropin beta in mouse breast carcinoma.
For many breast cancer patients, human chorionic gonadotropin beta (hCGbeta), which is a subunit of a hormone produced by the trophoblast and is essential for maintaining pregnancy, is expressed in the breast cancer cells. However, the mechanism as to how the CGbeta in cell affects the cancer development is not very clear. Mouse breast carcinoma 4T1 with stably hCGbeta expression (4T1-hCGbeta) was established and transplanted into the Balb/c mouse abdominal mammary gland. hCGbeta suppressed breast cancer cell viability in vitro, and dramatically inhibited tumor growth and attenuated tumor vessel formation in vivo. An 86-88% reduction in tumor volume in animals injected with breast cancer expressing hCGbeta, as opposed to those injected with breast cancer without hCGbeta expression, was observed. The production of p21 was promoted by hCGbeta, whereas the Cdk2 was decreasing. These indicate that p21 signal pathway is involved in this process. Significant apoptosis was also detected in hCGbeta-expressing breast cancer cells as well as the enhancement of Bax protein expression. Moreover, hCGbeta blocked the blood vessels formation by inhibiting the expression of MMP9 and VEGF. Further hormone secretion analyses show that the anti-tumor activity induced by hCGbeta is not related to the endocrine function.
Shi
Shu-Qun
SQ
Molecular Immunology Group, State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100080, People's Republic of China.
Xu
Li
L
Zhao
Gang
G
Yang
Ying
Y
Peng
Jing-Pian
JP
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000096:biosynthesis* / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D002352:Carrier Proteins; D018997:Chorionic Gonadotropin, beta Subunit, Human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C415788:Mtbp protein, mouse; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D051357:Cyclin-Dependent Kinase 2; D020780:Matrix Metalloproteinase 9