Abstract
An abnormal stimulation of cAMP signaling cascade has been implicated in various human carcinomas. Since the agents activating G(s)α-mediated signaling pathways have been shown to increase in vitro proliferation of prostate cancer cells, present studies examined the G(s)α-mediated signaling in tumorigenicity and invasiveness of PC-3M prostate cancer cells. PC-3M cells were stably transfected with plasmids containing either wild type (G(s)α-WT) or constitutively active (gsp mutant of G(s)α or G(s)α-QL) cDNAs. The stable transfectants were then tested for: (1) colony formation in soft agar; (2) cell migration and penetration of basement matrix in an in vitro invasion assay; and (3) the ability to form tumors and metastases in nude mice. PC-3M cells expressing G(s)α-QL protein displayed 15-fold increase in their ability to migrate and penetrate the basement membrane as compared to parental PC-3M cells or those expressing G(s)α-WT. G(s)α-QL transfectants also displayed a dramatically greater rate of growth in soft agar, and greater tumorigenicity and metastasis forming ability when orthotopically implanted in nude mice. All mice receiving PC-3M cells produced primary tumors within 5 weeks after implantation. However, the cells expressing G(s)α-QL displayed a significantly faster tumor growth as assessed by prostate weight (greater than 20-fold as compared to PC-3M cells), and produced metastases in kidneys, lymph nodes, blood vessels, bowel mesentery and intestine. Interestingly, expression of G(s)α-WT reduced the ability of PC-3M cells to form tumors in nude mice. These results suggest that persistent activation of G(s)α-mediated signaling cascade can dramatically accelerate tumorigenesis and metastasizing ability of prostate cancer cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3376-3382 |
| Number of pages | 7 |
| Journal | Oncogene |
| Volume | 18 |
| Issue number | 22 |
| DOIs | |
| State | Published - Jun 3 1999 |
| Externally published | Yes |
Fingerprint
Keywords
- G(s)α
- Invasiveness
- Prostate cancer
- Tumorigenicity
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
Cite this
Constitutive activation of stimulatory guanine nucleotide binding protein (G(s)αQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells. / Chien, J.; Wong, E.; Nikes, E.; Noble, M. J.; Pantazis, C. G.; Shah, G. V.
In: Oncogene, Vol. 18, No. 22, 03.06.1999, p. 3376-3382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Constitutive activation of stimulatory guanine nucleotide binding protein (G(s)αQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells
AU - Chien, J.
AU - Wong, E.
AU - Nikes, E.
AU - Noble, M. J.
AU - Pantazis, C. G.
AU - Shah, G. V.
PY - 1999/6/3
Y1 - 1999/6/3
N2 - An abnormal stimulation of cAMP signaling cascade has been implicated in various human carcinomas. Since the agents activating G(s)α-mediated signaling pathways have been shown to increase in vitro proliferation of prostate cancer cells, present studies examined the G(s)α-mediated signaling in tumorigenicity and invasiveness of PC-3M prostate cancer cells. PC-3M cells were stably transfected with plasmids containing either wild type (G(s)α-WT) or constitutively active (gsp mutant of G(s)α or G(s)α-QL) cDNAs. The stable transfectants were then tested for: (1) colony formation in soft agar; (2) cell migration and penetration of basement matrix in an in vitro invasion assay; and (3) the ability to form tumors and metastases in nude mice. PC-3M cells expressing G(s)α-QL protein displayed 15-fold increase in their ability to migrate and penetrate the basement membrane as compared to parental PC-3M cells or those expressing G(s)α-WT. G(s)α-QL transfectants also displayed a dramatically greater rate of growth in soft agar, and greater tumorigenicity and metastasis forming ability when orthotopically implanted in nude mice. All mice receiving PC-3M cells produced primary tumors within 5 weeks after implantation. However, the cells expressing G(s)α-QL displayed a significantly faster tumor growth as assessed by prostate weight (greater than 20-fold as compared to PC-3M cells), and produced metastases in kidneys, lymph nodes, blood vessels, bowel mesentery and intestine. Interestingly, expression of G(s)α-WT reduced the ability of PC-3M cells to form tumors in nude mice. These results suggest that persistent activation of G(s)α-mediated signaling cascade can dramatically accelerate tumorigenesis and metastasizing ability of prostate cancer cells.
AB - An abnormal stimulation of cAMP signaling cascade has been implicated in various human carcinomas. Since the agents activating G(s)α-mediated signaling pathways have been shown to increase in vitro proliferation of prostate cancer cells, present studies examined the G(s)α-mediated signaling in tumorigenicity and invasiveness of PC-3M prostate cancer cells. PC-3M cells were stably transfected with plasmids containing either wild type (G(s)α-WT) or constitutively active (gsp mutant of G(s)α or G(s)α-QL) cDNAs. The stable transfectants were then tested for: (1) colony formation in soft agar; (2) cell migration and penetration of basement matrix in an in vitro invasion assay; and (3) the ability to form tumors and metastases in nude mice. PC-3M cells expressing G(s)α-QL protein displayed 15-fold increase in their ability to migrate and penetrate the basement membrane as compared to parental PC-3M cells or those expressing G(s)α-WT. G(s)α-QL transfectants also displayed a dramatically greater rate of growth in soft agar, and greater tumorigenicity and metastasis forming ability when orthotopically implanted in nude mice. All mice receiving PC-3M cells produced primary tumors within 5 weeks after implantation. However, the cells expressing G(s)α-QL displayed a significantly faster tumor growth as assessed by prostate weight (greater than 20-fold as compared to PC-3M cells), and produced metastases in kidneys, lymph nodes, blood vessels, bowel mesentery and intestine. Interestingly, expression of G(s)α-WT reduced the ability of PC-3M cells to form tumors in nude mice. These results suggest that persistent activation of G(s)α-mediated signaling cascade can dramatically accelerate tumorigenesis and metastasizing ability of prostate cancer cells.
KW - G(s)α
KW - Invasiveness
KW - Prostate cancer
KW - Tumorigenicity
UR - http://www.scopus.com/inward/record.url?scp=0005982599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0005982599&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1202690
DO - 10.1038/sj.onc.1202690
M3 - Article
C2 - 10362358
AN - SCOPUS:0005982599
VL - 18
SP - 3376
EP - 3382
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 22
ER -