A role for ADAM12 in breast tumor progression and stromal cell apoptosis.
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A role for ADAM12 in breast tumor progression and stromal cell apoptosis. / Kveiborg, Marie; Frohlich, Camilla; Albrechtsen, Reidar; Tischler, Verena; Dietrich, Nikolaj; Holck, Peter; Kronqvist, Pauliina; Rank, Fritz; Mercurio, Arthur M; Wewer, Ulla M.
In: Cancer Research, Vol. 65, No. 11, 2005, p. 4754-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A role for ADAM12 in breast tumor progression and stromal cell apoptosis.
AU - Kveiborg, Marie
AU - Frohlich, Camilla
AU - Albrechtsen, Reidar
AU - Tischler, Verena
AU - Dietrich, Nikolaj
AU - Holck, Peter
AU - Kronqvist, Pauliina
AU - Rank, Fritz
AU - Mercurio, Arthur M
AU - Wewer, Ulla M.
N1 - Keywords: 3T3-L1 Cells; ADAM Proteins; Animals; Apoptosis; Breast; Breast Neoplasms; CHO Cells; Cell Growth Processes; Cricetinae; Disease Progression; Humans; Membrane Proteins; Metalloendopeptidases; Mice; Mice, Transgenic; Stromal Cells
PY - 2005
Y1 - 2005
N2 - As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.
AB - As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.
U2 - 10.1158/0008-5472.CAN-05-0262
DO - 10.1158/0008-5472.CAN-05-0262
M3 - Journal article
C2 - 15930294
VL - 65
SP - 4754
EP - 4761
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 11
ER -
ID: 5035074