Protein kinase C alpha expression in breast and ovarian cancer.
In recent years research has focused on the development of specific, targeted drugs to treat cancer. One approach has been to block intracellular signaling proteins, such as protein kinase C alpha (PKC-alpha). To help support the rationale for clinical studies of a PKC-alpha-targeted therapy in breast and ovarian cancers, we reviewed publications studying PKC-alpha expression in these tumors. Since these investigations were mostly performed in cell lines, we supplemented this review with some preliminary findings from studies examining PKC-alpha expression in tumor tissue biopsies obtained from patients with breast and ovarian cancer. Based on the reviewed publications using representative cell lines and our preliminary findings on tumor tissue of patients with breast cancer, we infer that PKC-alpha levels may especially be increased in breast cancer patients with low or negative estrogen receptor (ER) levels. Thus, clinical studies determining efficacy of selective or specific inhibitors of PKC-alpha should include determination of ER status in order to help answer whether blocking PKC-alpha in patients with low or absent ER can result in clinical benefit.
Lahn
Michael
M
Divison of Oncology Product Development, Lilly Research Laboratories, Eli Lilly, Indianapolis, IN 46285, USA. MichaLahn@aol.com
Köhler
Gabriele
G
Sundell
Karen
K
Su
Chen
C
Li
Shuyu
S
Paterson
Blake M
BM
Bumol
Thomas F
TF
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D054735:Phosphorothioate Oligonucleotides; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D011960:Receptors, Estrogen / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D011960:Receptors, Estrogen; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C488084:aprinocarsen