Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma and their association with metastasis.

Caceres, Carme; Morote, J.; Torres, Irianna; Rodríguez-Vallejo, José M.; González, Jazmín De Anda; Reventós, Jaume

doi:10.3892/ijo.14.2.367

Cited by 18 publications

(16 citation statements)

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“…The ERBB2 (her-2/neu) oncogene (17q21.1) is in the vicinity of one of our minimal overlapping regions. Whereas amplification of ERBB2 is frequently found in breast cancers (reviewed in Alers and van Dekken, 1996;van Dekken et al, 1997), the role of ERBB2 in prostate cancer remains somewhat controversial (Bubendorf et al, 1999;Ross et al, 1997;Schwartz et al, 1999). Recently, a cross-talk between the ERBB2 tyrosine kinase and the androgen receptor signal transduction pathways during prostate cancer progression towards androgen-independent disease was described (Craft et al, 1999).…”

Section: Chromosomal Gainsmentioning

confidence: 99%

“…Gain of chromosome 7p12-p21 and 7q11.3-q33 has been detected by CGH analysis in (lymph node) metastases (Cher et al, 1996). Chromosome arm 7p12 contains the EGFR proto-oncogene, a gene possibly involved in prostate cancer (Schwartz et al, 1999) and other human neoplasms. Furthermore, the MET proto-oncogene, which maps to 7q31.1, is expressed in the majority of both primary tumors and metastases (Pisters et al, 1995).…”

Section: Chromosomal Gainsmentioning

confidence: 99%

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Identification of Genetic Markers for Prostatic Cancer Progression

Alers

Rochat

Krijtenburg

et al. 2000

Laboratory Investigation

164

126

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SUMMARY:Despite the high incidence of prostate cancer, only limited data are available on genes or chromosomes specifically involved in its initiation and progression. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded, tissues at different times in prostatic tumor progression to screen the tumor genome for gains and losses. Our panel included specimens derived from 56 different patients: 23 patients with primary, prostate-confined carcinomas; 18 patients with regional lymph node metastases; and 15 patients with distant metastases. Chromosome arms that most frequently showed losses, included 13q (55%), 8p (48%), 6q (43%), 5q (32%), 16q (25%), 18q (20%), 2q (18%), 4q (18%), 10q (18%), and Y (16%). Gains were often seen of chromosome arms 8q (36%), 17q (23%), Xq (23%), 7q (21%), 3q (18%), 9q (18%), 1q (16%), Xp (16%). Furthermore, specific high-level amplifications, eg, of 1q21, 1q25, and Xq12 to q13, were found in metastatic cancers. A significant accumulation of genetic changes in distant metastases was observed, eg, loss of 10q (p ϭ 0.03) and gain of 7q (p ϭ 0.03) sequences. In addition, investigation of a potential biomarker identified in previous studies by our group, ie, extra copies of #7 and/or #8, revealed a high prevalence of 7pq and/or 8q gain in the distant metastases (p ϭ 0.02). Importantly, gains were observed more frequently in tumors derived from progressors after radical prostatectomy, than in nonprogressors (mean time of follow-up, 74 months). Specifically, gain of chromosome 7pq and/or 8q sequences appeared an accurate discriminator between the progressors and nonprogressors. Multivariate analysis showed a significant correlation between progressive disease and the number of chromosomes with gains. This correlation also held true when stage (p ϭ 0.007) or grade (p ϭ 0.002) were taken into account. Likewise, this applied for gain of chromosome 7pq and/or 8q sequences (p ϭ 0.03 and p ϭ 0.005 for stage or grade, respectively). Additionally, an increase in the number of chromosomes with gains per case was related to a decrease in biochemical progression-free survival (P trend Ͻ0.001). More specifically, the gain of 7pq and/or 8q sequences markedly reduced the biochemical progression-free survival (p Ͻ 0.001). In conclusion, this study has, firstly, documented the spectrum of chromosomal alterations in subsequent stages of prostate cancer, a number of which had not been described previously. It allowed us to identify chromosomal regions related to advanced tumor stage, ie, loss of 10q24 and gain of 7q11.2 and/or 7q31 sequences. Secondly, gain of 7pq and/or 8q was identified as a potential genetic discriminator between progressors and nonprogressors after radical surgery. (Lab Invest 2000, 80:931-942). P rostate cancer is the most commonly diagnosed, male noncutaneous malignancy and the second leading cause of cancer-related death in men in Western industrialized countries. Its incidence is continuously rising, with over 200,000 new cases diagnosed each year, r...

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Section: Chromosomal Gainsmentioning

confidence: 99%

Section: Chromosomal Gainsmentioning

confidence: 99%

Identification of Genetic Markers for Prostatic Cancer Progression

Alers

Rochat

Krijtenburg

et al. 2000

Laboratory Investigation

164

126

View full text Add to dashboard Cite

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“…Recent studies have shown that EGFR can directly bind to and phosphorylate the p85 subunit of PI3-K resulting in PI3-K activation (Soler et al, 1994;Tiganis et al, 1999;Imukai et al, 2001). EGFR expression is significantly increased in androgen-independent prostate cancer cells and EGFR plays a significant role in the prognosis of prostate cancer (Gil-Diez de Medina et al, 1998;Schwartz et al, 1999;Agarwal, 2000). In addition, MDA-MB-468 cells overexpress EGFR and the EGF can stimulate the growth of these cells (Balmer et al, 2001).…”

Section: Mda-mb-468mentioning

confidence: 99%

Apoptosis signaling by the novel compound 3-Cl-AHPC involves increased EGFR proteolysis and accompanying decreased phosphatidylinositol 3-kinase and AKT kinase activities

et al. 2004

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The threonine and serine protein kinase AKT plays a major role in inhibiting apoptosis in a number of malignant cell types including prostate and breast carcinoma. Activation of AKT is a complex process involving translocation to the plasma membrane and phosphorylation of serine and threonine amino-acid residues. We now report that the novel compound 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), induces apoptosis in breast and prostate carcinoma cells and inhibits AKT activity in these cells. Overexpression of a constitutively activated AKT inhibits 3-Cl-AHPC-mediated apoptosis. Decrease in AKT activity occurs through 3-Cl-AHPC inhibition of phosphatidylinositol 3 kinase (PI3-K) activity. 3-Cl-AHPC inhibits PI3-K activity by enhancing epidermal growth factor receptor (EGFR) proteolysis and thus inhibiting EGFR association with the p85 subunit of PI3-K. 3-Cl-AHPCmediated decrease in PI3-K activity results in the reduced synthesis of phosphatidylinositol 3,4 bisphosphate and phosphatidylinositol 3,4,5 triphosphate with the subsequent inhibition of integrin-linked kinase activity and serine-473 phosphorylation of AKT. Overexpression of EGFR results in increased AKT activity and inhibition of 3-Cl-AHPC-mediated decrease in AKT activation, AKT activity and 3-Cl-AHPC-mediated apoptosis. Inhibition of AKT activity by this compound results in the inability of AKT to phosphorylate and inactivate the proapoptotic forkhead transcription factor.

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“…Ligand binding to the extracellular domain of the erbB receptor results in phosphorylation of tyrosine residues in the tyrosine kinase (TK) domain, which mediates cell proliferation, survival, angiogenesis, and metastasis (3)(4)(5). Additionally, the magnitude of erbB expression has been consistently shown to be an adverse prognostic determinant in patients with carcinomas of the breast (6 -10), ovary (11,12), prostate (13,14), stomach (15,16), head and neck (17), lung (18), brain (19), and melanoma (20), and has served in part as the rationale for developing various therapeutic strategies against erbB (21).…”

Section: Introductionmentioning

confidence: 99%

Administration of CI-1033, an Irreversible Pan-erbB Tyrosine Kinase Inhibitor, Is Feasible on a 7-Day On, 7-Day Off Schedule

Calvo

Tolcher

Hammond

et al. 2004

Clinical Cancer Research

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Purpose: To determine the maximum tolerated dose of administrating CI-1033, an oral 4-anilinoquinazoline that irreversibly inhibits the tyrosine kinase domain of all erbB subfamilies, on an intermittent schedule, and assess the interaction of CI-1033 with food on the pharmacokinetic behavior.Experimental Design: Escalating doses of CI-1033 from a dose level of 300 mg/day for 7 days every other week were administered to patients with advanced solid malignancies. Plasma concentration-time data sets from all evaluable patients were used to develop a population pharmacokinetic model. Noncompartmental methods were used to independently assess the effect of a high-fat meal on CI-1033 absorption and bioavailability.Results: Twenty-four patients were treated with 69 twenty-eight day courses. The incidence of unacceptable toxicity, principally diarrhea and skin rash, was observed at the 300 mg/day dose level. At the 250 mg/day level, toxicity was manageable, and protracted administration was feasi- Conclusions: The recommended dose on this schedule is 250 mg/day. Its tolerability and the biological relevance of concentrations achieved at the maximal tolerated dose warrant consideration of disease-directed evaluations. This intermittent treatment schedule can be used without regard to meals.

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Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma and their association with metastasis.

Cited by 18 publications

References 0 publications

Identification of Genetic Markers for Prostatic Cancer Progression

Identification of Genetic Markers for Prostatic Cancer Progression

Apoptosis signaling by the novel compound 3-Cl-AHPC involves increased EGFR proteolysis and accompanying decreased phosphatidylinositol 3-kinase and AKT kinase activities

Administration of CI-1033, an Irreversible Pan-erbB Tyrosine Kinase Inhibitor, Is Feasible on a 7-Day On, 7-Day Off Schedule

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