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      Molecular Mechanism of Progesterone-Induced Apoptosis in Human Breast Cancer T47D Cells

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      https://www.riss.kr/link?id=A104744714

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      다국어 초록 (Multilingual Abstract)

      Progesterone plays an essential role in the development and differentiation of the mammary gland. Although it is well established that progesterone regulates cellular proliferation and differentiation, the molecular mechanisms of progesterone-mediated anticancer effects remain unclear. Therefore, the aim of the present study was to determine how progesterone regulates the growth and viability of T47D human breast cancer cells. In this study, the proliferation of T47D cells was inhibited after 48 hours of incubation in the presence of 10μM progesterone. The progesterone-treated T47D cells also exhibited hallmarks of apoptosis including DNA fragmentation and nuclear morphological changes detected with DAPI staining. Also, PR-A and PR-B progesterone receptor expression was decreased in a dose-dependent manner. Moreover, progesterone significantly decreased the expression of p53, cyclin D1, and CDK4, while it increased the expression of p27. These results clearly demonstrate high doses of progesterone induce T47D human breast cancer cell apoptosis and suppress proliferation by inhibiting the expression of key cell cycle regulators. (Cancer Prev Res 13, 177-183, 2008)
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      Progesterone plays an essential role in the development and differentiation of the mammary gland. Although it is well established that progesterone regulates cellular proliferation and differentiation, the molecular mechanisms of progesterone-mediated...

      Progesterone plays an essential role in the development and differentiation of the mammary gland. Although it is well established that progesterone regulates cellular proliferation and differentiation, the molecular mechanisms of progesterone-mediated anticancer effects remain unclear. Therefore, the aim of the present study was to determine how progesterone regulates the growth and viability of T47D human breast cancer cells. In this study, the proliferation of T47D cells was inhibited after 48 hours of incubation in the presence of 10μM progesterone. The progesterone-treated T47D cells also exhibited hallmarks of apoptosis including DNA fragmentation and nuclear morphological changes detected with DAPI staining. Also, PR-A and PR-B progesterone receptor expression was decreased in a dose-dependent manner. Moreover, progesterone significantly decreased the expression of p53, cyclin D1, and CDK4, while it increased the expression of p27. These results clearly demonstrate high doses of progesterone induce T47D human breast cancer cell apoptosis and suppress proliferation by inhibiting the expression of key cell cycle regulators. (Cancer Prev Res 13, 177-183, 2008)

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      참고문헌 (Reference)

      1 Oren, M., "p53: the ultimate tumor suppressor gene?" 6 : 3169-3176, 1992

      2 Horwitz, K.B., "Variant T47D human breast cancer cells with high progesterone-receptor levels despite estrogen and antiestrogen resistance" 28 : 633-642, 1982

      3 Kastner, P., "Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B" 9 : 1603-1614, 1990

      4 Gronemeyer, H., "Transcription activation by estrogen and progesterone receptors" 25 : 89-123, 1991

      5 Hurd, C., "Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and antiestrogens in breast cancer cells" 15 : 991-995, 1997

      6 Kester, H.A., "Prolonged progestin treatment induces the promoter of CDK inhibitor p21 Cip1,Waf1 through activation of p53 in human breast and endometrial tumor cells" 284 : 264-273, 2003

      7 Clarke, C.L., "Progestin regulation of cellular proliferation" 11 : 266-301, 1990

      8 DiLorenzo, D., "Progestin regulation of alkaline phosphatase in the human breast cancer cell line T47D" 51 : 4470-4475, 1991

      9 Moore, M.R., "Progestin inhibition of cell death in human breast cancer cell lines" 98 : 218-227, 2006

      10 Moore, M.R., "Progestin effects on long-term growth, death, and Bcl-xL in breast cancer cells" 277 : 650-654, 2000

      1 Oren, M., "p53: the ultimate tumor suppressor gene?" 6 : 3169-3176, 1992

      2 Horwitz, K.B., "Variant T47D human breast cancer cells with high progesterone-receptor levels despite estrogen and antiestrogen resistance" 28 : 633-642, 1982

      3 Kastner, P., "Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B" 9 : 1603-1614, 1990

      4 Gronemeyer, H., "Transcription activation by estrogen and progesterone receptors" 25 : 89-123, 1991

      5 Hurd, C., "Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and antiestrogens in breast cancer cells" 15 : 991-995, 1997

      6 Kester, H.A., "Prolonged progestin treatment induces the promoter of CDK inhibitor p21 Cip1,Waf1 through activation of p53 in human breast and endometrial tumor cells" 284 : 264-273, 2003

      7 Clarke, C.L., "Progestin regulation of cellular proliferation" 11 : 266-301, 1990

      8 DiLorenzo, D., "Progestin regulation of alkaline phosphatase in the human breast cancer cell line T47D" 51 : 4470-4475, 1991

      9 Moore, M.R., "Progestin inhibition of cell death in human breast cancer cell lines" 98 : 218-227, 2006

      10 Moore, M.R., "Progestin effects on long-term growth, death, and Bcl-xL in breast cancer cells" 277 : 650-654, 2000

      11 Formby, B., "Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53" 28 : 360-369, 1998

      12 Horita, K., "Progesterone induces apoptosis in malignant mesothelioma cells" 21 : 3871-3874, 2001

      13 Graham, J.D., "Physiological action of progesterone in target tissues" 18 : 502-519, 1997

      14 Alkhalaf, M., "Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone" 179 : 55-62, 2003

      15 Tsai, M.J., "Molecular mechanisms of action of steroid/thyroid receptor superfamily members" 63 : 451-486, 1994

      16 Musgrove, E.A., "Mechanisms of cyclin-dependent kinase inactivation by progestins" 18 : 1812-1825, 1998

      17 Dinda, S., "Inhibition of proliferation of T47D human breast cancer cells: alterations in progesterone receptor and p53 tumor suppressor protein" 175 : 81-89, 1997

      18 Hurd, C., "Hormonal regulation of the p53 tumor suppressor protein in T47D human breast carcinoma cell line" 270 : 28507-28510, 1995

      19 Vienonen, A., "Expression of progesterone receptor isoforms A and B is differentially regulated by estrogen in different breast cancer cell lines" 80 : 307-313, 2002

      20 Santen, R.J., "Endocrine treatment of breast cancer in women" 11 : 221-265, 1990

      21 Hissom, J.R., "Effects of progestins, estrogens, and antihormones on growth and lactate dehydrogenase in the human breast cancer cell line T47D" 125 : 418-423, 1989

      22 Alban, P., "Differential regulation of retinoblastoma protein by hormonal and antihormonal agents in T47D breast cancer cells" 77 : 135-141, 2001

      23 Richer, J.K., "Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells" 277 : 5209-5218, 2002

      24 Franke, H., "Differential effects of progestogens on breast cancer cell lines" 46S1 : S55-S58, 2003

      25 Musgrove, E.A., "Cyclin D1 overexpression induces progestin resistance in T-47D breast cancer cells despite p27 (Kip1) association with cyclin E-Cdk2" 276 : 47675-47683, 2001

      26 Sonnenschein, C., "Control of cell proliferation of human breast MCF7 cells; serum and estrogen resistant variants" 6 : 373-381, 1994

      27 Groshong, S.D., "Biphasic regulation of breast cancer cell growth by progesterone: role of the cyclin-dependent kinase inhibitors, p21 and p27 (Kip1)" 11 : 1593-1607, 1997

      28 Yu, S., "Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840" 82 : 445-451, 2001

      29 Musgrove, E.A., "Antiprogestin inhibition of cell cycle progression in T-47D breast cancer cells is accompanied by induction of the cyclin- dependent kinase inhibitor p21" 11 : 54-66, 1997

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2022 평가예정 재인증평가 신청대상 (재인증)
      2019-01-01 평가 등재학술지 선정 (계속평가) KCI등재
      2018-12-01 평가 등재후보로 하락 (계속평가) KCI등재후보
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2013-10-14 학술지명변경 외국어명 : Cancer Prevention Research -> Journal of Cancer Prevention KCI등재
      2012-10-15 학회명변경 영문명 : Korean Association of Cancer Prevention -> Korean Society of Cancer Preveniton KCI등재
      2011-04-04 학술지명변경 외국어명 : Journal of Korean Association of Cancer Prevention -> Cancer Prevention Research KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2008-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2007-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2005-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.22 0.22 0.18
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.15 0.12 0.405 0.13
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